Paucimannosylation

The term "paucimannose" (occasionally spelled as "pauci-mannose") was coined in the early 1990s glycobiology literature. Paucimannose utilises the prefix "pauci" meaning few or small in Latin and the suffix "mannose" indicating glycans involving mannose-terminating glycans.

The phrases protein paucimannosylation and paucimannosidic proteins are commonly used in the literature to describe paucimannose-modified glycoproteins displaying intact structural and functional integrity. In contrast, the oligosaccharides themselves are often referred to as paucimannosidic, low mannose, and truncated glycans or other less conventional nomenclature.

A simple shorthand nomenclature has been proposed as a convenient way to name the individual paucimannosidic glycan structures, e.g. M3F denotes Man₃GlcNAc₂Fuc₁.{{Cite journal |last1=Loke |first1=Ian |last2=Østergaard |first2=Ole |last3=Heegaard |first3=Niels H.H. |last4=Packer |first4=Nicolle H. |last5=Thaysen-Andersen |first5=Morten |date=August 2017 |title=Paucimannose-Rich N-glycosylation of Spatiotemporally Regulated Human Neutrophil Elastase Modulates Its Immune Functions*. |journal=Molecular & Cellular Proteomics |volume=16 |issue=8 |pages=1507–1527 |doi=10.1074/mcp.m116.066746 |doi-access=free |pmid=28630087 |pmc=5546201 |s2cid=19548998 |issn=1535-9476}}{{Cite journal |last1=Ugonotti |first1=Julian |last2=Chatterjee |first2=Sayantani |last3=Thaysen-Andersen |first3=Morten |date=June 2021 |title=Structural and functional diversity of neutrophil glycosylation in innate immunity and related disorders |url=|journal=Molecular Aspects of Medicine |volume=79 |article-number=100882 |doi=10.1016/j.mam.2020.100882 |pmid=32847678 |s2cid=221345832 |issn=0098-2997}}{{Cite journal |last1=Ugonotti |first1=Julian |last2=Kawahara |first2=Rebeca |last3=Loke |first3=Ian |last4=Zhu |first4=Yuqi |last5=Chatterjee |first5=Sayantani |last6=Tjondro |first6=Harry C |last7=Sumer-Bayraktar |first7=Zeynep |last8=Neelamegham |first8=Sriram |last9=Thaysen-Andersen |first9=Morten |date=2021-10-18 |title=N-acetyl-β-D-hexosaminidases mediate the generation of paucimannosidic proteins via a putative noncanonical truncation pathway in human neutrophils |url=|journal=Glycobiology |volume=32 |issue=3 |pages=218–229 |doi=10.1093/glycob/cwab108 |pmid=34939086 |pmc=8966476 |issn=1460-2423}}

Paucimannosidic glycans span the base composition Man_1-3GlcNAc₂.{{Cite journal |last1=Yan |first1=Shi |last2=Wilson |first2=Iain B. H. |last3=Paschinger |first3=Katharina |date=June 2015 |title=Comparison of RP-HPLC modes to analyse the N-glycome of the free-living nematodePristionchus pacificus |url=|journal=Electrophoresis |volume=36 |issue=11–12 |pages=1314–1329 |doi=10.1002/elps.201400528 |pmid=25639343 |pmc=4422755 |issn=0173-0835}} Additional modifications with Fuc, Xyl and/or Galactose (Gal) are common in mammals ref, plants{{Cite journal |last1=Wilson |first1=I. B.H. |last2=Zeleny |first2=R. |last3=Kolarich |first3=D. |last4=Staudacher |first4=E. |last5=Stroop |first5=C. J.M. |last6=Kamerling |first6=J. P. |last7=Altmann |first7=F. |date=2001-04-01 |title=Analysis of Asn-linked glycans from vegetable foodstuffs: widespread occurrence of Lewis a, core 1,3-linked fucose and xylose substitutions |journal=Glycobiology |volume=11 |issue=4 |pages=261–274 |doi=10.1093/glycob/11.4.261 |pmid=11358875 |issn=0959-6658|doi-access=free }} and invertebrates, respectively.{{Cite journal |last=Schachter |first=Harry |date=August 2009 |title=Paucimannose N-glycans in Caenorhabditis elegans and Drosophila melanogaster |url=|journal=Carbohydrate Research |volume=344 |issue=12 |pages=1391–1396 |doi=10.1016/j.carres.2009.04.028 |pmid=19515361 |issn=0008-6215}} Paucimannosidic glycans expressed by insects and nematodes are particularly rich in structural diversity.

Paucimannosylation has been extensively studied and documented in insects, nematodes and plants over the past decades. The paucimannosidic proteins are constitutively and broadly expressed across tissues in these organisms under normal physiology.{{Cite book |title=Essentials of glycobiology |date=2009 |publisher=Cold Spring Harbor Laboratory Press |others=Ajit Varki |isbn=978-0-87969-770-9 |edition=2nd |location=Cold Spring Harbor, N.Y. |oclc=195765240}} It is widely recognised that paucimannosylation is a central component of the glycoproteome in these "lower" organisms. Recently, paucimannosylation was reported to form an unconventional type of protein N-glycosylation in vertebrates. It has been proposed that "higher" species including humans, rodents and other mammals use paucimannosylation in a more tissue- and context-restricted manner in pathophysiological conditions including cancer,{{Cite journal |last1=Chatterjee |first1=Sayantani |last2=Lee |first2=Ling Y. |last3=Kawahara |first3=Rebeca |last4=Abrahams |first4=Jodie L. |last5=Adamczyk |first5=Barbara |last6=Anugraham |first6=Merrina |last7=Ashwood |first7=Christopher |last8=Sumer-Bayraktar |first8=Zeynep |last9=Briggs |first9=Matthew T. |last10=Chik |first10=Jenny H. L. |last11=Everest-Dass |first11=Arun |date=2019-10-16 |title=Protein Paucimannosylation Is an EnrichedN-Glycosylation Signature of Human Cancers |url=|journal=Proteomics |volume=19 |issue=21–22 |pages=1900010 |doi=10.1002/pmic.201900010 |pmid=31419058 |hdl=10072/388125 |s2cid=201018579 |issn=1615-9853|hdl-access=free }} pathogen infection, inflammation and stemness.{{Cite journal |last1=Zipser |first1=Birgit |last2=Diestel |first2=Simone |last3=Bello-DeOcampo |first3=Diana |last4=Tai |first4=Mei-Hui |last5=Schmitz |first5=Brigitte |date=November 2012 |title=Mannitou monoclonal antibody uniquely recognizes paucimannose, a marker for human cancer, stemness and inflammation |url=|journal=Journal of Biotechnology |volume=161 |pages=5 |doi=10.1016/j.jbiotec.2012.07.160 |issn=0168-1656}}

Paucimannosidic glycans form the main component of the N-glycome of insects such as Drosophila melanogaster.{{Cite journal |last1=Aoki |first1=Kazuhiro |last2=Perlman |first2=Mindy |last3=Lim |first3=Jae-Min |last4=Cantu |first4=Rebecca |last5=Wells |first5=Lance |last6=Tiemeyer |first6=Michael |date=March 2007 |title=Dynamic Developmental Elaboration of N-Linked Glycan Complexity in the Drosophila melanogaster Embryo |journal=Journal of Biological Chemistry |volume=282 |issue=12 |pages=9127–9142 |doi=10.1074/jbc.m606711200 |pmid=17264077 |issn=0021-9258|doi-access=free }} Glycoprofiling of the venom component of the western honeybee, Apis mellifera, identified that paucimannosylation is a common modification of key proteins including hyaluronidase and phospholipase.{{Cite journal |last1=KUBELKA |first1=Viktoria |last2=ALTMANN |first2=Friedrich |last3=STAUDACHER |first3=Erika |last4=TRETTER |first4=Verena |last5=März |first5=Leopold |last6=HARD |first6=Karl |last7=KAMERLING |first7=Johannis P. |last8=VLIEGENTHART |first8=Johannes F. G. |date=May 1993 |title=Primary structures of the N-linked carbohydrate chains from honeybee venom phospholipase A2 |journal=European Journal of Biochemistry |volume=213 |issue=3 |pages=1193–1204 |doi=10.1111/j.1432-1033.1993.tb17870.x |pmid=8504812 |issn=0014-2956|doi-access=free }}{{Cite journal |last1=Kubelka |first1=Viktoria |last2=Altmann |first2=Friedrich |last3=Mrz |first3=Leopold |date=February 1995 |title=The asparagine-linked carbohydrate of honeybee venom hyaluronidase |url=|journal=Glycoconjugate Journal |volume=12 |issue=1 |pages=77–83 |doi=10.1007/bf00731872 |pmid=7795417 |s2cid=1543607 |issn=0282-0080}}

Insect cells lines are frequently utilised for recombinant expression of mammalian glycoproteins, which therefore are decorated with paucimannosidic glycans e.g. mouse interferon-β,{{Cite journal |last1=Misaki |first1=Ryo |last2=Nagaya |first2=Hidekazu |last3=Fujiyama |first3=Kazuhito |last4=Yanagihara |first4=Itaru |last5=Honda |first5=Takeshi |last6=Seki |first6=Tatsuji |date=November 2003 |title=N-linked glycan structures of mouse interferon-β produced by Bombyx mori larvae |url=|journal=Biochemical and Biophysical Research Communications |volume=311 |issue=4 |pages=979–986 |doi=10.1016/j.bbrc.2003.10.094 |pmid=14623278 |bibcode=2003BBRC..311..979M |issn=0006-291X}} human IgG₁{{Cite journal |last1=Park |first1=Enoch Y. |last2=Ishikiriyama |first2=Motoki |last3=Nishina |first3=Takuya |last4=Kato |first4=Tatsuya |last5=Yagi |first5=Hirokazu |last6=Kato |first6=Koichi |last7=Ueda |first7=Hiroshi |date=January 2009 |title=Human IgG1 expression in silkworm larval hemolymph using BmNPV bacmids and its N-linked glycan structure |url=|journal=Journal of Biotechnology |volume=139 |issue=1 |pages=108–114 |doi=10.1016/j.jbiotec.2008.09.013 |pmid=18984019 |hdl=10297/5175 |s2cid=13070665 |issn=0168-1656|hdl-access=free }} and calf alkaline phosphatase.{{Cite journal |last1=Nomura |first1=Tsuyoshi |last2=Suganuma |first2=Masatoshi |last3=Higa |first3=Yukiko |last4=Kataoka |first4=Yukiko |last5=Funaguma |first5=Shunsuke |last6=Okazaki |first6=Hironobu |last7=Suzuki |first7=Takeo |last8=Kobayashi |first8=Isao |last9=Sezutsu |first9=Hideki |last10=Fujiyama |first10=Kazuhito |date=February 2015 |title=Improvement of glycosylation structure by suppression of β-N-acetylglucosaminidases in silkworm |url=|journal=Journal of Bioscience and Bioengineering |volume=119 |issue=2 |pages=131–136 |doi=10.1016/j.jbiosc.2014.07.012 |pmid=25193875 |issn=1389-1723}}

The model organism Caenorhabditis elegans classified under the phylum Nematoda is amongst the most studied invertebrate species in glycobiology. The literature clearly documents a repertoire of nematodal paucimannosidic glycans.{{Cite journal |last1=Paschinger |first1=Katharina |last2=Yan |first2=Shi |last3=Wilson |first3=Iain B. H. |date=2019-03-12 |title=N-glycomic Complexity in Anatomical Simplicity: Caenorhabditis elegans as a Non-model Nematode? |journal=Frontiers in Molecular Biosciences |volume=6 |page=9 |doi=10.3389/fmolb.2019.00009 |pmid=30915340 |pmc=6422873 |issn=2296-889X|doi-access=free }} Another model nematode, Pristionchus pacificus, was also documented to express common nematodal paucimannosidic glycans.

Parasitic nematodes such as Haemonchus contortus have been reported to carry paucimannosidic glycans conjugated to an intestinal microsomal aminopeptidase.{{Cite journal |last1=Smith |first1=Trevor S |last2=Graham |first2=Margaret |last3=Munn |first3=Edward A |last4=Newton |first4=Susan E |last5=Knox |first5=David P |last6=Coadwell |first6=W.John |last7=McMichael-Phillips |first7=Danielle |last8=Smith |first8=Howard |last9=Smith |first9=W.David |last10=Oliver |first10=Joanne J |date=April 1997 |title=Cloning and characterization of a microsomal aminopeptidase from the intestine of the nematode Haemonchus contortus |url=|journal=Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology |volume=1338 |issue=2 |pages=295–306 |doi=10.1016/s0167-4838(96)00204-x |pmid=9128148 |issn=0167-4838}} In addition, there have been reports documenting the expression of paucimannosidic glycans by others parasitic nematodes such as Ascaris suum,{{Cite journal |last1=Pöltl |first1=Gerald |last2=Kerner |first2=Denise |last3=Paschinger |first3=Katharina |last4=Wilson |first4=Iain B. H. |date=2006-12-20 |title=N-Glycans of the porcine nematode parasite Ascaris suum are modified with phosphorylcholine and core fucose residues |url=|journal=FEBS Journal |volume=274 |issue=3 |pages=714–726 |doi=10.1111/j.1742-4658.2006.05615.x |pmid=17181538 |pmc=2850173 |issn=1742-464X}} Heligmosomoides polygyrus{{Cite journal |last1=Hewitson |first1=James P. |last2=Filbey |first2=Kara J. |last3=Grainger |first3=John R. |last4=Dowle |first4=Adam A. |last5=Pearson |first5=Mark |last6=Murray |first6=Janice |last7=Harcus |first7=Yvonne |last8=Maizels |first8=Rick M. |date=2011-09-30 |title=Heligmosomoides polygyrus Elicits a Dominant Nonprotective Antibody Response Directed against Restricted Glycan and Peptide Epitopes |url=|journal=The Journal of Immunology |volume=187 |issue=9 |pages=4764–4777 |doi=10.4049/jimmunol.1004140 |pmid=21964031 |pmc=4306209 |issn=0022-1767}} and Trichuris suis.{{Cite journal |last1=Wilson |first1=Iain B. H. |last2=Paschinger |first2=Katharina |date=2015-12-09 |title=Sweet secrets of a therapeutic worm: mass-spectrometric N-glycomic analysis of Trichuris suis |url=|journal=Analytical and Bioanalytical Chemistry |volume=408 |issue=2 |pages=461–471 |doi=10.1007/s00216-015-9154-8 |pmid=26650734 |pmc=4712359 |issn=1618-2642}}

Most plant species studied to date are recognised to constitutively express paucimannosidic N-glycoproteins. The paucimannosidic N-glycoproteins are abundantly expressed in the vacuoles of plants such as the legume seeds of Lotus japonicus,{{Cite journal |last1=Dam |first1=Svend |last2=Thaysen-Andersen |first2=Morten |last3=Stenkjær |first3=Eva |last4=Lorentzen |first4=Andrea |last5=Roepstorff |first5=Peter |last6=Packer |first6=Nicolle H. |last7=Stougaard |first7=Jens |date=2013-06-25 |title=Combined N-Glycome and N-Glycoproteome Analysis of the Lotus japonicus Seed Globulin Fraction Shows Conservation of Protein Structure and Glycosylation in Legumes |url=|journal=Journal of Proteome Research |volume=12 |issue=7 |pages=3383–3392 |doi=10.1021/pr400224s |pmid=23799247 |issn=1535-3893}} the rice seeds and leaves of Oryza sativa.{{Cite journal |last1=Wang |first1=Xianghong |last2=Jiang |first2=Daiming |last3=Shi |first3=Jingni |last4=Yang |first4=Daichang |date=January 2017 |title=Expression of α-1,6-fucosyltransferase (FUT8) in rice grain and immunogenicity evaluation of plant-specific glycans |url=|journal=Journal of Biotechnology |volume=242 |pages=111–121 |doi=10.1016/j.jbiotec.2016.12.017 |pmid=28013072 |issn=0168-1656}} Literature has provided evidence for plant-specific paucimannosidic glycan structures modified with Xyl and Fuc. Such structures are found across the broad Streptophyta (land plants) and Chlorophyta (green algae) clade and in diatoms such as Phaeodactylum tricornutum. Less reported bixylosylated paucimannosidic glycans have also been documented.{{Cite journal |last1=Mathieu-Rivet |first1=Elodie |last2=Scholz |first2=Martin |last3=Arias |first3=Carolina |last4=Dardelle |first4=Flavien |last5=Schulze |first5=Stefan |last6=Le Mauff |first6=François |last7=Teo |first7=Gavin |last8=Hochmal |first8=Ana Karina |last9=Blanco-Rivero |first9=Amaya |last10=Loutelier-Bourhis |first10=Corinne |last11=Kiefer-Meyer |first11=Marie-Christine |date=November 2013 |title=Exploring the N-glycosylation Pathway in Chlamydomonas reinhardtii Unravels Novel Complex Structures |journal=Molecular & Cellular Proteomics |volume=12 |issue=11 |pages=3160–3183 |doi=10.1074/mcp.m113.028191 |doi-access=free |pmid=23912651 |pmc=3820931 |issn=1535-9476}}

Paucimannosidic proteins have been reported in vertebrates such as quail,{{Cite journal |last1=HASE |first1=Sumihiro |last2=OKAWA |first2=Kazunobu |last3=IKENAKA |first3=Tokuji |date=1982 |title=Identification of the Trimannosyl-Chitobiose Structure in Sugar Moieties of Japanese Quail Ovomucoid1 |url=|journal=The Journal of Biochemistry |volume=91 |issue=2 |pages=735–737 |doi=10.1093/oxfordjournals.jbchem.a133748 |pmid=7068587 |issn=1756-2651}} chicken{{Cite journal |last1=ALONSO |first1=Josefa María |last2=BOULENGUER |first2=Patrick |last3=WIERUSZESKI |first3=Jean-Michel |last4=LEROY |first4=Yves |last5=MONTREUIL |first5=Jean |last6=FOURNET |first6=Bernard |date=2005-03-03 |title=Microheterogeneity and structures of neutral glycans present in quail ovomucoid |journal=European Journal of Biochemistry |volume=177 |issue=1 |pages=187–197 |doi=10.1111/j.1432-1033.1988.tb14361.x-i2 |pmid=3181154 |issn=0014-2956|doi-access=free }} and in mammals, encompassing a limited diversity of paucimannosidic glycan structures. Early findings reported on paucimannosidic glycans on lysosomal glycoproteins in domestic animals.{{Cite journal |last1=Faid |first1=Valegh |last2=Evjen |first2=Gry |last3=Tollersrud |first3=Ole-Kristian |last4=Michalski |first4=Jean-Claude |last5=Morelle |first5=Willy |date=2006-01-31 |title=Site-specific glycosylation analysis of the bovine lysosomal α-mannosidase |journal=Glycobiology |volume=16 |issue=5 |pages=440–461 |doi=10.1093/glycob/cwj081 |pmid=16449350 |issn=1460-2423|doi-access=free }} and human tissues,{{Cite journal |last1=Howard |first1=D R |last2=Natowicz |first2=M |last3=Baenziger |first3=J U |date=September 1982 |title=Structural studies of the endoglycosidase H-resistant oligosaccharides present on human beta-glucuronidase. |journal=Journal of Biological Chemistry |volume=257 |issue=18 |pages=10861–10868 |doi=10.1016/s0021-9258(18)33904-8 |pmid=6809759 |s2cid=24105430 |issn=0021-9258|doi-access=free }} but have subsequently been found also to decorate non-lysosomal glycoproteins.{{Cite journal |last1=SUMIYOSHI |first1=Wataru |last2=NAKAKITA |first2=Shin-ichi |last3=HASEHIRA |first3=Kayo |last4=MIYANISHI |first4=Nobumitsu |last5=KUBO |first5=Yuhki |last6=KITA |first6=Takayoshi |last7=HIRABAYASHI |first7=Jun |date=2010-03-23 |title=Comprehensive Analysis ofN-Linked Oligosaccharides from Eggs of the Family Phasianidae |url=|journal=Bioscience, Biotechnology, and Biochemistry |volume=74 |issue=3 |pages=606–613 |doi=10.1271/bbb.90821 |pmid=20208342 |s2cid=44957115 |issn=0916-8451}}{{Cite journal |last1=Hanzawa |first1=Ken |last2=Suzuki |first2=Noriko |last3=Natsuka |first3=Shunji |date=2016-12-08 |title=Structures and developmental alterations ofN-glycans of zebrafish embryos |journal=Glycobiology |volume=27 |issue=3 |pages=228–245 |doi=10.1093/glycob/cww124 |pmid=27932382 |issn=0959-6658|doi-access=free }} Particularly, the granules of human neutrophils are a principal source of paucimannosidic proteins.{{Cite journal |last1=Olczak |first1=Mariusz |last2=Wątorek |first2=Wiesław |date=April 2002 |title=Structural analysis of N-glycans from human neutrophil azurocidin |url=|journal=Biochemical and Biophysical Research Communications |volume=293 |issue=1 |pages=213–219 |doi=10.1016/s0006-291x(02)00201-2 |pmid=12054586 |bibcode=2002BBRC..293..213O |issn=0006-291X}}{{Cite journal |last1=Ravnsborg |first1=Tina |last2=Houen |first2=Gunnar |last3=Højrup |first3=Peter |date=October 2010 |title=The glycosylation of myeloperoxidase |url=|journal=Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics |volume=1804 |issue=10 |pages=2046–2053 |doi=10.1016/j.bbapap.2010.07.001 |pmid=20621206 |issn=1570-9639}}{{Cite journal |last1=Tjondro |first1=Harry C. |last2=Ugonotti |first2=Julian |last3=Kawahara |first3=Rebeca |last4=Chatterjee |first4=Sayantani |last5=Loke |first5=Ian |last6=Chen |first6=Siyun |last7=Soltermann |first7=Fabian |last8=Hinneburg |first8=Hannes |last9=Parker |first9=Benjamin L. |last10=Venkatakrishnan |first10=Vignesh |last11=Dieckmann |first11=Regis |date=January 2021 |title=Hyper-truncated Asn355- and Asn391-glycans modulate the activity of neutrophil granule myeloperoxidase |journal=Journal of Biological Chemistry |volume=296 |article-number=100144 |doi=10.1074/jbc.ra120.016342 |pmid=33273015 |pmc=7857493 |issn=0021-9258|doi-access=free }} Paucimannosidic proteins were also observed in human monocytes and macrophages{{Cite journal |last1=Hinneburg |first1=Hannes |last2=Pedersen |first2=Jessica L |last3=Bokil |first3=Nilesh J |last4=Pralow |first4=Alexander |last5=Schirmeister |first5=Falko |last6=Kawahara |first6=Rebeca |last7=Rapp |first7=Erdmann |last8=Saunders |first8=Bernadette M |last9=Thaysen-Andersen |first9=Morten |date=2020-03-09 |title=High-resolution longitudinal N- and O-glycoprofiling of human monocyte-to-macrophage transition |url=|journal=Glycobiology |volume=30 |issue=9 |pages=679–694 |doi=10.1093/glycob/cwaa020 |pmid=32149347 |issn=1460-2423|hdl=10453/146548 |hdl-access=free }} and paucimannosidic immunoglycopeptides were found to be presented by SARS-CoV-2 challenged dendritic cells.{{cite journal |last1=Parker |first1=Robert |last2=Partridge |first2=Thomas |last3=Wormald |first3=Catherine |last4=Kawahara |first4=Rebeca |last5=Stalls |first5=Victoria |last6=Aggelakopoulou |first6=Maria |last7=Parker |first7=Jimmy |last8=Powell Doherty |first8=Rebecca |last9=Ariosa Morejon |first9=Yoanna |last10=Lee |first10=Esther |last11=Saunders |first11=Kevin |last12=Haynes |first12=Barton F. |last13=Acharya |first13=Priyamvada |last14=Thaysen-Andersen |first14=Morten |last15=Borrow |first15=Persephone |last16=Ternette |first16=Nicola |title=Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells |journal=Cell Reports |date=May 2021 |volume=35 |issue=8 |pages=109179 |biorxiv=10.1101/2020.08.19.255901 |doi=10.1016/j.celrep.2021.109179|pmid=34004174 |pmc=8116342 }} Species within other classes under Animalia related to vertebrates were also documented to express paucimannosidic proteins.{{Cite journal |last1=Yagi |first1=H. |last2=Nakagawa |first2=M. |last3=Takahashi |first3=N. |last4=Kondo |first4=S. |last5=Matsubara |first5=M. |last6=Kato |first6=K. |date=2007-11-13 |title=Neural complex-specific expression of xylosyl N-glycan in Ciona intestinalis |url=|journal=Glycobiology |volume=18 |issue=2 |pages=145–151 |doi=10.1093/glycob/cwm128 |pmid=18056652 |issn=0959-6658}} with some observations of unusual plant- and invertebrate-like paucimannosidic glycan structures

Despite receiving considerable focus, the glycobiological literature do not contain evidence for the presence of paucimannosidic proteins within Fungi. Fungal species within this kingdom are therefore considered devoid of protein paucimannosylation and instead carry high mannosylated N-glycoproteins comprising extended and branched mannose-decorated antennae.{{Citation |last=Ballou |first=Clinton E. |chapter=Isolation, characterization, and properties of Saccharomyces cerevisiae MNN mutants with nonconditional protein glycosylation defects |title=Gene Expression Technology |date=1990 |chapter-url=|series=Methods in Enzymology |volume=185 |pages=440–470 |publisher=Elsevier |doi=10.1016/0076-6879(90)85038-p |pmid=2199792 |isbn=9780121820862 }}{{Cite journal |last=Masuoka |first=James |date=April 2004 |title=Surface Glycans Candida albicans and Other Pathogenic Fungi: Physiological Roles, Clinical Uses, and Experimental Challenges |url=|journal=Clinical Microbiology Reviews |volume=17 |issue=2 |pages=281–310 |doi=10.1128/cmr.17.2.281-310.2004 |pmid=15084502 |pmc=387410 |issn=0893-8512}}

Similar to other N-linked glycan types, the biosynthesis of paucimannosidic proteins across most species has been documented to be facilitated by the actions of a limited set of glyco-enzymes including beta-N-acetylhexosaminidases (Hex) and alpha-mannosidases, through GnT-I-dependent and -independent truncation pathways.

Studies on insect cell lines and in vivo experiments on D. melanogaster have revealed active expression of Hexo1 and Hexo2, and, most importantly, the fused lobe (fdl) gene encoding fused ß-lobe (FDL), also known as GNase, an orthologue of A. thaliana and human Hex. FDL is expressed in high abundance in vesicles and the plasma membrane and has, unlike Hexo1 and Hexo2, been linked to fruit fly paucimannosidic protein production.{{Cite journal |last1=Altmann |first1=Friedrich |last2=Schwihla |first2=Herwig |last3=Staudacher |first3=Erika |last4=Glössl |first4=Josef |last5=März |first5=Leopold |date=July 1995 |title=Insect Cells Contain an Unusual, Membrane-bound β-N-Acetylglucosaminidase Probably Involved in the Processing of Protein N-Glycans |journal=Journal of Biological Chemistry |volume=270 |issue=29 |pages=17344–17349 |doi=10.1074/jbc.270.29.17344 |pmid=7615537 |issn=0021-9258|doi-access=free }}{{Cite journal |last1=Rosenbaum |first1=Erica E. |last2=Vasiljevic |first2=Eva |last3=Brehm |first3=Kimberley S. |last4=Colley |first4=Nansi Jo |date=2014-05-01 |title=Mutations in Four Glycosyl Hydrolases Reveal a Highly Coordinated Pathway for Rhodopsin Biosynthesis and N-Glycan Trimming in Drosophila melanogaster |journal=PLOS Genetics |volume=10 |issue=5 |pages=e1004349 |doi=10.1371/journal.pgen.1004349 |pmid=24785692 |pmc=4006722 |s2cid=5699432 |issn=1553-7404 |doi-access=free }}{{Cite journal |last1=Cattaneo |first1=F. |last2=Pasini |first2=M. E. |last3=Intra |first3=J. |last4=Matsumoto |first4=M. |last5=Briani |first5=F. |last6=Hoshi |first6=M. |last7=Perotti |first7=M. E. |date=2006-05-29 |title=Identification and expression analysis of Drosophilamelanogaster genes encoding β-hexosaminidases of the sperm plasma membrane |journal=Glycobiology |volume=16 |issue=9 |pages=786–800 |doi=10.1093/glycob/cwl007 |pmid=16733265 |issn=1460-2423|doi-access=free }}{{Cite journal |last1=Cattaneo |first1=F. |last2=Ogiso |first2=M. |last3=Hoshi |first3=M. |last4=Perotti |first4=M.-E. |last5=Pasini |first5=M.E. |date=August 2002 |title=Purification and characterization of the plasma membrane glycosidases of Drosophila melanogaster spermatozoa |url=|journal=Insect Biochemistry and Molecular Biology |volume=32 |issue=8 |pages=929–941 |doi=10.1016/s0965-1748(02)00031-0 |pmid=12110300 |bibcode=2002IBMB...32..929C |issn=0965-1748}} However, except for the well-studied D. melanogaster and other common insect model organisms, solid evidence for active involvement of Hex and/or the possible concerted usage of the GnT-I-independent pathway or alternative truncation pathways for paucimannosidic protein production remains unavailable across the diverse class of insects.

The model organism C. elegans is well studied; solid glycobiological literature have provided insights on the nematodal N-glycosylation machinery which shares many traits with other eukaryotic species.{{Cite journal |last1=Gutternigg |first1=Martin |last2=Kretschmer-Lubich |first2=Dorothea |last3=Paschinger |first3=Katharina |last4=Rendić |first4=Dubravko |last5=Hader |first5=Josef |last6=Geier |first6=Petra |last7=Ranftl |first7=Ramona |last8=Jantsch |first8=Verena |last9=Lochnit |first9=Günter |last10=Wilson |first10=Iain B.H. |date=September 2007 |title=Biosynthesis of Truncated N-Linked Oligosaccharides Results from Non-orthologous Hexosaminidase-mediated Mechanisms in Nematodes, Plants, and Insects |journal=Journal of Biological Chemistry |volume=282 |issue=38 |pages=27825–27840 |doi=10.1074/jbc.m704235200 |pmid=17636254 |pmc=2850174 |issn=0021-9258|doi-access=free }}{{Cite journal |last1=Paschinger |first1=Katharina |last2=Gutternigg |first2=Martin |last3=Rendić |first3=Dubravko |last4=Wilson |first4=Iain B.H. |date=August 2008 |title=The N-glycosylation pattern of Caenorhabditis elegans |url=|journal=Carbohydrate Research |volume=343 |issue=12 |pages=2041–2049 |doi=10.1016/j.carres.2007.12.018 |pmid=18226806 |issn=0008-6215}} C. elegans is known to produce paucimannosidic proteins via a GnT-I-dependent route in which GnT-I firstly produces GlcNAc-capped glycoprotein intermediates. Further processing by two Hex isoenzymes (HEX-2 and HEX-3) encoded by two C. elegans genes (hex-2, hex-3) generate the unsubstituted C. elegans paucimannosidic glycans.

Other glycoenzymes catalise further processing and structural diversity including α-Man II and α1,6- and α1,3-fucosyltransferases. Albeit less active, a GnT-I-independent α1,6-fucosyltransferase has also been observed for C. elegans,{{Cite journal |last1=Igarashi |first1=Kiyohiko |last2=Wada |first2=Masahisa |last3=Samejima |first3=Masahiro |date=2009 |title=Kinetic Analysis of Cellobiohydrolase: Quantification of Enzymatic Reaction at a Solid/Liquid Interface Applying the Concept of Surface Density |journal=Trends in Glycoscience and Glycotechnology |volume=21 |issue=117 |pages=13–22 |doi=10.4052/tigg.21.13 |issn=0915-7352|doi-access=free }}{{Cite journal |last1=Yan |first1=Shi |last2=Wang |first2=Huijie |last3=Schachter |first3=Harry |last4=Jin |first4=Chunsheng |last5=Wilson |first5=Iain B.H. |last6=Paschinger |first6=Katharina |date=October 2018 |title=Ablation of N-acetylglucosaminyltransferases in Caenorhabditis induces expression of unusual intersected and bisected N-glycans |url=|journal=Biochimica et Biophysica Acta (BBA) - General Subjects |volume=1862 |issue=10 |pages=2191–2203 |doi=10.1016/j.bbagen.2018.07.002 |pmid=29981898 |pmc=6173287 |issn=0304-4165}} indicating that both the GnT-I-dependent and -independent pathways may contribute to the formation of paucimannosidic N-glycoproteins in worms. However, the biosynthetic processes underpinning the unusual non-sugar and core-modified paucimannosidic N-glycans in C. elegans remain to be elucidated.

Hexosaminidases (Hex) are important glycoside hydrolases for the generation of plant-specific paucimannosidic proteins across Plantae. HEXO1-HEXO3 have been reported to be key mediators of paucimannose expression in various plant species including Nicotiana benthamiana,{{Cite journal |last1=Shin |first1=Yun-Ji |last2=Castilho |first2=Alexandra |last3=Dicker |first3=Martina |last4=Sádio |first4=Flavio |last5=Vavra |first5=Ulrike |last6=Grünwald-Gruber |first6=Clemens |last7=Kwon |first7=Tae-Ho |last8=Altmann |first8=Friedrich |last9=Steinkellner |first9=Herta |last10=Strasser |first10=Richard |date=2016-08-11 |title=Reduced paucimannosidicN-glycan formation by suppression of a specific β-hexosaminidase fromNicotiana benthamiana |url=|journal=Plant Biotechnology Journal |volume=15 |issue=2 |pages=197–206 |doi=10.1111/pbi.12602 |pmid=27421111 |pmc=5259580 |issn=1467-7644}} A.thaliana{{Cite journal |last1=Strasser |first1=Richard |last2=Bondili |first2=Jayakumar Singh |last3=Schoberer |first3=Jennifer |last4=Svoboda |first4=Barbara |last5=Liebminger |first5=Eva |last6=Glössl |first6=Josef |last7=Altmann |first7=Friedrich |last8=Steinkellner |first8=Herta |last9=Mach |first9=Lukas |date=2007-07-20 |title=Enzymatic Properties and Subcellular Localization of Arabidopsis β-N-Acetylhexosaminidases |url=|journal=Plant Physiology |volume=145 |issue=1 |pages=5–16 |doi=10.1104/pp.107.101162 |pmid=17644627 |pmc=1976588 |s2cid=13573193 |issn=1532-2548}} and L. japonicus.{{Cite journal |last1=Pedersen |first1=Carina T. |last2=Loke |first2=Ian |last3=Lorentzen |first3=Andrea |last4=Wolf |first4=Sara |last5=Kamble |first5=Manoj |last6=Kristensen |first6=Sebastian K. |last7=Munch |first7=David |last8=Radutoiu |first8=Simona |last9=Spillner |first9=Edzard |last10=Roepstorff |first10=Peter |last11=Thaysen-Andersen |first11=Morten |date=2017-05-22 |title=N-glycan maturation mutants in Lotus japonicus for basic and applied glycoprotein research |journal=The Plant Journal |volume=91 |issue=3 |pages=394–407 |doi=10.1111/tpj.13570 |pmid=28407380 |s2cid=6370095 |issn=0960-7412|doi-access=free |bibcode=2017PlJ....91..394P }} Moreover, α1,3-fucosyltransferase (FUT11/12){{Cite journal |last1=Strasser |first1=Richard |last2=Schoberer |first2=Jennifer |last3=Jin |first3=Chunsheng |last4=Glössl |first4=Josef |last5=Mach |first5=Lukas |last6=Steinkellner |first6=Herta |date=March 2006 |title=Molecular cloning and characterization ofArabidopsis thalianaGolgi α-mannosidase II, a key enzyme in the formation of complex N-glycans in plants |url=|journal=The Plant Journal |volume=45 |issue=5 |pages=789–803 |doi=10.1111/j.1365-313x.2005.02648.x |pmid=16460512 |issn=0960-7412}} and β1,2-xylosyltransferase{{Cite journal |last1=Strasser |first1=R. |last2=Altmann |first2=F. |last3=Mach |first3=L. |last4=Glössl |first4=J. |last5=Steinkellner |first5=H. |date=2004-02-20 |title=Generation of Arabidopsis thaliana plants with complex N-glycans lacking β1,2-linked xylose and core α1,3-linked fucose |url=|journal=FEBS Letters |volume=561 |issue=1–3 |pages=132–136 |doi=10.1016/s0014-5793(04)00150-4 |pmid=15013764 |bibcode=2004FEBSL.561..132S |s2cid=83647511 |issn=0014-5793}} as well as α-mannosidase II{{Cite journal |last1=Ghosh |first1=Sumit |last2=Meli |first2=Vijaykumar S. |last3=Kumar |first3=Anil |last4=Thakur |first4=Archana |last5=Chakraborty |first5=Niranjan |last6=Chakraborty |first6=Subhra |last7=Datta |first7=Asis |date=2010-10-28 |title=The N-glycan processing enzymes α-mannosidase and β-D-N-acetylhexosaminidase are involved in ripening-associated softening in the non-climacteric fruits of capsicum |url=|journal=Journal of Experimental Botany |volume=62 |issue=2 |pages=571–582 |doi=10.1093/jxb/erq289 |pmid=21030387 |pmc=3003805 |issn=1460-2431}} were also reported to play critical roles in the generation of the paucimannosidic proteins expressed by plants.

In humans, the Hex-mediated GnT-I-dependent truncation pathway is known to facilitate, at least in some tissues including neutrophils, the production of paucimannosidic proteins. Human Hex isoenzymes are assembled with alpha and beta subunits encoded by the HEXA and HEXB genes, respectively.{{Cite journal |last1=Hepbildikler |first1=Stefan T. |last2=Sandhoff |first2=Roger |last3=Kölzer |first3=Melanie |last4=Proia |first4=Richard L. |last5=Sandhoff |first5=Konrad |date=January 2002 |title=Physiological Substrates for Human Lysosomal β-Hexosaminidase S |journal=Journal of Biological Chemistry |volume=277 |issue=4 |pages=2562–2572 |doi=10.1074/jbc.m105457200 |pmid=11707436 |issn=0021-9258|doi-access=free }} From these two subunits, isoenzymes such as Hex A (one alpha and one beta subunit), Hex B (two beta subunits) and Hex S (two alpha subunits) are generated. Both Hex A and Hex B are reported to play important functional roles in human, particularly in the lysosomal degradation of gangliosides. Recently, both HEXA and HEXB were documented to mediate protein paucimannosylation in human neutrophils and may therefore also be the main driver for the elevated production of paucimannosidic proteins during cancer development. Recent in vitro observations have suggested other noncanonical truncation pathways with direct core fucosylation of paucimannosidic proteins in vertebrates, but this remains to be validated Hex A and Hex B isoenzymes are mainly present in the azurophilic granules of human neutrophils as a result of a proposed targeting-by-timing mechanism that supposedly directs these enzymes to this compartment during neutrophil development.{{Cite journal |last1=Cowland |first1=Jack B. |last2=Borregaard |first2=Niels |date=2016-08-25 |title=Granulopoiesis and granules of human neutrophils |url=|journal=Immunological Reviews |volume=273 |issue=1 |pages=11–28 |doi=10.1111/imr.12440 |pmid=27558325 |s2cid=28294497 |issn=0105-2896}} Recently, granule-specific glycosylation was shown in neutrophils featuring prominent paucimannosylation in the azurophilic granules an observation that was suggested to arise from a "glycosylation-by-timing" mechanism yet to be documented.{{Cite journal |last1=Venkatakrishnan |first1=Vignesh |last2=Dieckmann |first2=Regis |last3=Loke |first3=Ian |last4=Tjondro |first4=Harry |last5=Chatterjee |first5=Sayantani |last6=Bylund |first6=Johan |last7=Thaysen-Andersen |first7=Morten |last8=Karlsson |first8=Niclas G. |last9=Karlsson-Bengtsson |first9=Anna |date=2020-04-02 |title=Glycan analysis of human neutrophil granules implicates a maturation-dependent glycosylation machinery |journal=The Journal of Biological Chemistry|volume=295 |issue=36 |pages=12648–12660 |doi=10.1074/jbc.RA120.014011|biorxiv=10.1101/2020.04.02.021394 |pmid=32665399 |pmc=7476722 |s2cid=215403886 |doi-access=free }} More widely across vertebrate species, the biosynthesis of paucimannosidic proteins remains largely unstudied.

The function of protein paucimannosylation remains largely unexplored in vertebrates. Recent literature however has emerged demonstrating that paucimannosylation play roles in mediating pathophysiological processes such as in inflammation, pathogen infection, cancer and in the development of stem cells and in normal homeostasis. For example, elevated expression of paucimannosidic proteins was shown in Mycobacterium tuberculosis infected macrophages,{{Cite book |last=M |first=Hare, NJ Lee, LY Loke, I Britton, WJ Saunders, BM Thaysen-Andersen |title=Mycobacterium tuberculosis Infection Manipulates the Glycosylation Machinery and the N-Glycoproteome of Human Macrophages and Their Microparticles |date=2017-01-06 |oclc=1105695513}} during preclampsia{{Cite journal |last1=Robajac |first1=Dragana |last2=Vanhooren |first2=Valerie |last3=Masnikosa |first3=Romana |last4=Miković |first4=Željko |last5=Mandić |first5=Vesna |last6=Libert |first6=Claude |last7=Nedić |first7=Olgica |date=February 2016 |title=Preeclampsia transforms membrane N-glycome in human placenta |journal=Experimental and Molecular Pathology |volume=100 |issue=1 |pages=26–30 |doi=10.1016/j.yexmp.2015.11.029 |pmid=26655437 |issn=0014-4800}} and on Tamm-Horsfall proteins secreted by human urothelial cells during urinary tract infections suggesting the involvement of paucimannosylation in those conditions.{{Cite journal |last1=Pak |first1=Joanne |last2=Pu |first2=Yongbing |last3=Zhang |first3=Zhong-Ting |last4=Hasty |first4=David L. |last5=Wu |first5=Xue-Ru |date=March 2001 |title=Tamm-Horsfall Protein Binds to Type 1 Fimbriated Escherichia coli and Prevents E. coli from Binding to Uroplakin Ia and Ib Receptors |journal=Journal of Biological Chemistry |volume=276 |issue=13 |pages=9924–9930 |doi=10.1074/jbc.m008610200 |pmid=11134021 |issn=0021-9258|doi-access=free }} Additionally, sputum from individuals suffering from cystic fibrosis and airway infections were also observed to be rich in paucimannosidic proteins.{{Cite journal |last1=Venkatakrishnan |first1=Vignesh |last2=Thaysen-Andersen |first2=Morten |last3=Chen |first3=Sharon C A |last4=Nevalainen |first4=Helena |last5=Packer |first5=Nicolle H |date=2014-09-04 |title=Cystic fibrosis and bacterial colonization define the sputum N-glycosylation phenotype |journal=Glycobiology |volume=25 |issue=1 |pages=88–100 |doi=10.1093/glycob/cwu092 |pmid=25190359 |issn=0959-6658|doi-access=free }}{{Cite journal |last1=Everest-Dass |first1=Arun V |last2=Jin |first2=Dayong |last3=Thaysen-Andersen |first3=Morten |last4=Nevalainen |first4=Helena |last5=Kolarich |first5=Daniel |last6=Packer |first6=Nicolle H |date=2012-07-24 |title=Comparative structural analysis of the glycosylation of salivary and buccal cell proteins: innate protection against infection by Candida albicans |journal=Glycobiology |volume=22 |issue=11 |pages=1465–1479 |doi=10.1093/glycob/cws112 |pmid=22833316 |issn=1460-2423|doi-access=free }} Furthermore, paucimannosylation was reported to be prominent features of human neutrophils {{Cite journal |last1=Loke |first1=Ian |last2=Packer |first2=Nicolle |last3=Thaysen-Andersen |first3=Morten |date=2015-08-12 |title=Complementary LC-MS/MS-Based N-Glycan, N-Glycopeptide, and Intact N-Glycoprotein Profiling Reveals Unconventional Asn71-Glycosylation of Human Neutrophil Cathepsin G |journal=Biomolecules |volume=5 |issue=3 |pages=1832–1854 |doi=10.3390/biom5031832 |pmid=26274980 |pmc=4598777 |issn=2218-273X|doi-access=free }} and in monocytes and macrophages. Recent literature have also demonstrated elevated signatures of paucimannosidic proteins associated with a range of human cancers including brain,{{Cite journal |last1=Becker |first1=Yvonne |last2=Förster |first2=Sarah |last3=Gielen |first3=Gerrit H. |last4=Loke |first4=Ian |last5=Thaysen-Andersen |first5=Morten |last6=Laurini |first6=Christine |last7=Wehrand |first7=Kristin |last8=Pietsch |first8=Torsten |last9=Diestel |first9=Simone |date=2019-07-08 |title=Paucimannosidic glycoepitopes inhibit tumorigenic processes in glioblastoma multiforme |url=|journal=Oncotarget |volume=10 |issue=43 |pages=4449–4465 |doi=10.18632/oncotarget.27056 |pmid=31320997 |pmc=6633888 |issn=1949-2553}} breast,{{Cite journal |last1=Lee |first1=Ling Y. |last2=Thaysen-Andersen |first2=Morten |last3=Baker |first3=Mark S. |last4=Packer |first4=Nicolle H. |last5=Hancock |first5=William S. |last6=Fanayan |first6=Susan |date=2014-09-11 |title=Comprehensive N-Glycome Profiling of Cultured Human Epithelial Breast Cells Identifies Unique Secretome N-Glycosylation Signatures Enabling Tumorigenic Subtype Classification |url=|journal=Journal of Proteome Research |volume=13 |issue=11 |pages=4783–4795 |doi=10.1021/pr500331m |pmid=25210975 |issn=1535-3893}} blood, melanoma,{{Cite journal |last1=Abrahams |first1=Jodie L. |last2=Campbell |first2=Matthew P. |last3=Packer |first3=Nicolle H. |date=2017-09-13 |title=Building a PGC-LC-MS N-glycan retention library and elution mapping resource |url=|journal=Glycoconjugate Journal |volume=35 |issue=1 |pages=15–29 |doi=10.1007/s10719-017-9793-4 |pmid=28905148 |s2cid=3885305 |issn=0282-0080|doi-access=free }} non-melanoma,{{Citation |title=Squamous cell carcinoma and basal cell carcinoma of the skin |date=2007-11-15 |url=|work=Textbook of Surgical Oncology |pages=327–334 |publisher=CRC Press |doi=10.3109/9780203003220-30 |isbn=978-0-429-21406-6 }} liver,{{Cite journal |last1=Hinneburg |first1=Hannes |last2=Korać |first2=Petra |last3=Schirmeister |first3=Falko |last4=Gasparov |first4=Slavko |last5=Seeberger |first5=Peter H. |last6=Zoldoš |first6=Vlatka |last7=Kolarich |first7=Daniel |date=April 2017 |title=Unlocking Cancer Glycomes from Histopathological Formalin-fixed and Paraffin-embedded (FFPE) Tissue Microdissections |journal=Molecular & Cellular Proteomics |volume=16 |issue=4 |pages=524–536 |doi=10.1074/mcp.m116.062414 |doi-access=free |pmid=28122943 |pmc=5383776 |issn=1535-9476}} ovarian{{Cite journal |last1=Everest-Dass |first1=Arun V. |last2=Briggs |first2=Matthew T. |last3=Kaur |first3=Gurjeet |last4=Oehler |first4=Martin K. |last5=Hoffmann |first5=Peter |last6=Packer |first6=Nicolle H. |date=September 2016 |title=N-glycan MALDI Imaging Mass Spectrometry on Formalin-Fixed Paraffin-Embedded Tissue Enables the Delineation of Ovarian Cancer Tissues |journal=Molecular & Cellular Proteomics |volume=15 |issue=9 |pages=3003–3016 |doi=10.1074/mcp.m116.059816 |doi-access=free |pmid=27412689 |pmc=5013313 |issn=1535-9476}} and prostate cancers.{{Cite journal |last1=Kawahara |first1=Rebeca |last2=Ortega |first2=Fabio |last3=Rosa-Fernandes |first3=Livia |last4=Guimarães |first4=Vanessa |last5=Quina |first5=Daniel |last6=Nahas |first6=Willian |last7=Schwämmle |first7=Veit |last8=Srougi |first8=Miguel |last9=Leite |first9=Katia R.M. |last10=Thaysen-Andersen |first10=Morten |last11=Larsen |first11=Martin R. |date=2018-09-04 |title=Distinct urinary glycoprotein signatures in prostate cancer patients |url=|journal=Oncotarget |volume=9 |issue=69 |pages=33077–33097 |doi=10.18632/oncotarget.26005 |pmid=30237853 |pmc=6145689 |issn=1949-2553}} Enriched paucimannosidic glycoepitopes were found in the tumours when compared to the adjacent non-tumour tissues. Literature have also reported the presence of paucimannosylation in embryonic stem cells{{Cite book |last=Jarmo |first=Satomaa, Tero Heiskanen, Annamari Mikkola, Milla Olsson, Cia Blomqvist, Maria Tiittanen, Minna Jaatinen, Taina Aitio, Olli Olonen, Anne Helin, Jari Hiltunen, Jukka Natunen, Jari Tuuri, Timo Otonkoski, Timo Saarinen, Juhani Laine |title=The N-glycome of human embryonic stem cells |date=2009-06-02 |publisher=BioMed Central Ltd |oclc=808635211}} and neuronal stem cells,{{Cite journal |last1=Dahmen |first1=Ann-Christine |last2=Fergen |first2=Marie-Therese |last3=Laurini |first3=Christine |last4=Schmitz |first4=Brigitte |last5=Loke |first5=Ian |last6=Thaysen-Andersen |first6=Morten |last7=Diestel |first7=Simone |date=2015-04-28 |title=Paucimannosidic glycoepitopes are functionally involved in proliferation of neural progenitor cells in the subventricular zone |url=|journal=Glycobiology |volume=25 |issue=8 |pages=869–880 |doi=10.1093/glycob/cwv027 |pmid=25922361 |issn=0959-6658}} suggesting potential functional role(s) in these cells. Notably, deficiency of hexosaminidases results in clinically significant Tay-Sachs and Sandhoff diseases, which also implicates Hex and paucimannosidic proteins in those conditions.

Endogenous and exogenous binding partners of mammalian paucimannosidic glycans have been suggested, including the macrophage mannose receptor (CD206) and dectin-2. Other putative endogenous paucimannosidic protein receptors such as dectin-1, DC-SIGN and DC-SIGNR have been proposed, but experimental support is still lacking. Exogeneous binders of paucimannosidic glycans such as the Escherichia coli FimH{{Cite journal |last1=Taganna |first1=Joemar |last2=de Boer |first2=Arjen R. |last3=Wuhrer |first3=Manfred |last4=Bouckaert |first4=Julie |date=2011-01-19 |title=Glycosylation changes as important factors for the susceptibility to urinary tract infection |journal=Biochemical Society Transactions |volume=39 |issue=1 |pages=349–354 |doi=10.1042/bst0390349 |pmid=21265802 |issn=0300-5127}} and P. aeruginosa PA-IIL{{Cite journal |last1=Marotte |first1=Karine |last2=Sabin |first2=Charles |last3=Préville |first3=Cathy |last4=Moumé-Pymbock |first4=Myriam |last5=Wimmerová |first5=Michaela |last6=Mitchell |first6=Edward P. |last7=Imberty |first7=Anne |last8=Roy |first8=René |date=2007-09-10 |title=X-ray Structures and Thermodynamics of the Interaction of PA-IIL fromPseudomonas aeruginosa with Disaccharide Derivatives |url=|journal=ChemMedChem |volume=2 |issue=9 |pages=1328–1338 |doi=10.1002/cmdc.200700100 |pmid=17623286 |s2cid=9113181 |issn=1860-7179}} were also reported to play important roles in the adhesion and pathophysiology of these opportunistic pathogens.

In D. melanogaster, FDL-deficient mutants showed paucimannose-deficiency and, notably, caused locomotion defects in fruit flies, indicating that Hex and/or paucimannosidic proteins are involved, via elusive pathways, in essential fruit fly processes.{{Cite journal |last1=Léonard |first1=Renaud |last2=Rendić |first2=Dubravko |last3=Rabouille |first3=Catherine |last4=Wilson |first4=Iain B.H. |last5=Préat |first5=Thomas |last6=Altmann |first6=Friedrich |date=February 2006 |title=The Drosophila fused lobes Gene Encodes an N-Acetylglucosaminidase Involved in N-Glycan Processing |journal=Journal of Biological Chemistry |volume=281 |issue=8 |pages=4867–4875 |doi=10.1074/jbc.m511023200 |pmid=16339150 |issn=0021-9258|doi-access=free }} As expected, the less-consequential monoallelic fdl mutation was shown to result in reduced paucimannosidic protein formation and caused a non-lethal, but still severe phenotype, by halting the generation of peripheral long-term memory neurons. Impaired generation of peripheral long-term memory neurons was also observed for fruit fly fdl and MgatI null mutations, which, in turn, resulted in infertility and locomotion defects. The lack of fucosylated paucimannosidic glycans was proposed to contribute to neuronal impairment in both fdl and Mgat1 mutants. The importance of fucosylated paucimannosidic glycans was supported by a study reporting that mutations in the FucT6 gene encoding the D. melanogaster α1,6-fucosyltransferase resulted in an impaired fruit fly immune response towards parasitic infections.{{Cite journal |last1=Mortimer |first1=Nathan T. |last2=Kacsoh |first2=Balint Z. |last3=Keebaugh |first3=Erin S. |last4=Schlenke |first4=Todd A. |date=2012-07-19 |title=Mgat1-dependent N-glycosylation of Membrane Components Primes Drosophila melanogaster Blood Cells for the Cellular Encapsulation Response |journal=PLOS Pathogens |volume=8 |issue=7 |pages=e1002819 |doi=10.1371/journal.ppat.1002819 |pmid=22829770 |pmc=3400557 |issn=1553-7374 |doi-access=free }} Taken together, these phenotypic observations suggest that the fruit fly paucimannosidic glycans, some of which overlap with the human repertoire, are pivotal in the development, immune function and survival processes of D. melanogaster. It was reported that T. castaneum abundantly expresses paucimannosidic proteins during its post-larval stages,{{Cite journal |last1=Walski |first1=Tomasz |last2=Van Damme |first2=Els J. M. |last3=Smargiasso |first3=Nicolas |last4=Christiaens |first4=Olivier |last5=De Pauw |first5=Edwin |last6=Smagghe |first6=Guy |date=2016-10-12 |title=Protein N-glycosylation and N-glycan trimming are required for postembryonic development of the pest beetle Tribolium castaneum |url=|journal=Scientific Reports |volume=6 |issue=1 |page=35151 |doi=10.1038/srep35151 |pmid=27731363 |pmc=5059678 |bibcode=2016NatSR...635151W |issn=2045-2322}} recapitulating findings from other studies proposing that paucimannosidic proteins are strongly regulated during early development. Thus, it is likely that paucimannosidic glycans conjugated to still unknown flour beetle carrier proteins, similar to those in nematodes and fruit flies, are vital for growth and survival processes of the flour beetle.

Expression of phosphocholine-modified and unsubstituted C. elegans paucimannosidic glycans is reportedly development stage-specific, implying important roles in nematodal development.{{Cite journal |last1=Cipollo |first1=John F. |last2=Awad |first2=Antoine M. |last3=Costello |first3=Catherine E. |last4=Hirschberg |first4=Carlos B. |date=July 2005 |title=N-Glycans of Caenorhabditis elegans Are Specific to Developmental Stages |journal=Journal of Biological Chemistry |volume=280 |issue=28 |pages=26063–26072 |doi=10.1074/jbc.m503828200 |pmid=15899899 |issn=0021-9258|doi-access=free }} In support, C. elegans hex-2 gene knock-out mutants displayed reduced paucimannosidic protein levels and altered sensitivity towards nematotoxic lectins relative to wild-type worms, a correlation suggesting involvement of paucimannosidic proteins in key C. elegans survival processes.{{Cite journal |last1=Yan |first1=Shi |last2=Bleuler-Martinez |first2=Silvia |last3=Plaza |first3=David Fernando |last4=Künzler |first4=Markus |last5=Aebi |first5=Markus |last6=Joachim |first6=Anja |last7=Razzazi-Fazeli |first7=Ebrahim |last8=Jantsch |first8=Verena |last9=Geyer |first9=Rudolf |last10=Wilson |first10=Iain B.H. |last11=Paschinger |first11=Katharina |date=August 2012 |title=Galactosylated Fucose Epitopes in Nematodes |journal=Journal of Biological Chemistry |volume=287 |issue=34 |pages=28276–28290 |doi=10.1074/jbc.m112.353128 |pmid=22733825 |pmc=3436517 |issn=0021-9258|doi-access=free }} Functionally, phosphocholine-containing paucimannosidic glycans were demonstrated to display immune-modulating roles in parasitic nematodes.{{Cite journal |last1=Hewitson |first1=James P. |last2=Harcus |first2=Yvonne M. |last3=Curwen |first3=Rachel S. |last4=Dowle |first4=Adam A. |last5=Atmadja |first5=Agnes K. |last6=Ashton |first6=Peter D. |last7=Wilson |first7=Alan |last8=Maizels |first8=Rick M. |date=July 2008 |title=The secretome of the filarial parasite, Brugia malayi: Proteomic profile of adult excretory–secretory products |url=|journal=Molecular and Biochemical Parasitology |volume=160 |issue=1 |pages=8–21 |doi=10.1016/j.molbiopara.2008.02.007 |pmid=18439691 |issn=0166-6851}} Paucimannosidic glycans were suggested to play roles in the nematodal innate immune system by impacting the nematode's ability to fight and survive pathogenic bacteria{{Citation |last1=Shi |first1=Hui |date=2006 |url=|pages=359–389 |publisher=Elsevier |last2=Tan |first2=Jenny |last3=Schachter |first3=Harry|title=Functional Glycomics |chapter=N-Glycans Are Involved in the Response of Caenorhabditis elegans to Bacterial Pathogens |series=Methods in Enzymology |volume=417 |doi=10.1016/s0076-6879(06)17022-6 |pmid=17132514 |isbn=9780121828226 }}

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{{DEFAULTSORT:Paucimannosylation}}

Category:Post-translational modification

Category:Glycobiology

Category:Glycoproteins

Category:Carcinogenesis

Category:Inflammations

Category:Immune system

Category:Lysosomal storage diseases

Category:Nematology

Category:Biochemistry