PCLO
{{Short description|Protein-coding gene in humans}}
{{Infobox_gene}}
Protein piccolo is a protein that in humans is encoded by the PCLO gene.{{cite journal | vauthors = Cases-Langhoff C, Voss B, Garner AM, Appeltauer U, Takei K, Kindler S, Veh RW, De Camilli P, Gundelfinger ED, Garner CC | title = Piccolo, a novel 420 kDa protein associated with the presynaptic cytomatrix | journal = European Journal of Cell Biology | volume = 69 | issue = 3 | pages = 214–23 | date = Mar 1996 | pmid = 8900486 }}{{cite journal | vauthors = Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro | journal = DNA Research | volume = 5 | issue = 1 | pages = 31–9 | date = Feb 1998 | pmid = 9628581 | doi = 10.1093/dnares/5.1.31 | doi-access = free | citeseerx = 10.1.1.610.1181 }}{{cite web | title = Entrez Gene: PCLO piccolo (presynaptic cytomatrix protein)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27445}}
Function
Synaptic vesicles dock and fuse in the active zone of the plasma membrane at chemical synapses. The presynaptic cytoskeletal matrix (PCM), which is associated with the active zone and is situated between synaptic vesicles, is thought to be involved in maintaining the neurotransmitter release site in register with the postsynaptic reception apparatus. The cycling of synaptic vesicles is a multistep process involving a number of proteins (see MIM 603215). Among the components of the PCM that orchestrate these events are Bassoon (BSN; MIM 604020), RIM (RIMS1; MIM 606629), Oboe (RIMS2; MIM 606630), and Piccolo (PCLO).[supplied by OMIM]
Interactions
The protein product of PCLO called Piccolo has been shown to interact with number of proteins including GIT1,{{cite journal | vauthors = Kim S, Ko J, Shin H, Lee JR, Lim C, Han JH, Altrock WD, Garner CC, Gundelfinger ED, Premont RT, Kaang BK, Kim E | title = The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo | journal = The Journal of Biological Chemistry | volume = 278 | issue = 8 | pages = 6291–300 | date = Feb 2003 | pmid = 12473661 | doi = 10.1074/jbc.M212287200 | doi-access = free }} the F-actin-binding protein Abp1,{{Cite journal|last1=Fenster|first1=Steven D.|last2=Kessels|first2=Michael M.|last3=Qualmann|first3=Britta|last4=Chung|first4=Wook J.|last5=Nash|first5=Joanne|last6=Gundelfinger|first6=Eckart D.|last7=Garner|first7=Craig C.|date=2003-05-30|title=Interactions between Piccolo and the actin/dynamin-binding protein Abp1 link vesicle endocytosis to presynaptic active zones|journal=The Journal of Biological Chemistry|volume=278|issue=22|pages=20268–20277|doi=10.1074/jbc.M210792200|pmid=12654920|doi-access=free}} PRA1,{{Cite journal|last1=Fenster|first1=S. D.|last2=Chung|first2=W. J.|last3=Zhai|first3=R.|last4=Cases-Langhoff|first4=C.|last5=Voss|first5=B.|last6=Garner|first6=A. M.|last7=Kaempf|first7=U.|last8=Kindler|first8=S.|last9=Gundelfinger|first9=E. D.|date=2000-01-01|title=Piccolo, a presynaptic zinc finger protein structurally related to bassoon|journal=Neuron|volume=25|issue=1|pages=203–214|pmid=10707984|doi=10.1016/s0896-6273(00)80883-1|s2cid=10177138|doi-access=free}} TRIO,{{Cite journal|last1=Terry-Lorenzo|first1=Ryan T.|last2=Torres|first2=Viviana I.|last3=Wagh|first3=Dhananjay|last4=Galaz|first4=Jose|last5=Swanson|first5=Selene K.|last6=Florens|first6=Laurence|last7=Washburn|first7=Michael P.|last8=Waites|first8=Clarissa L.|last9=Gundelfinger|first9=Eckart D.|date=2016-01-01|title=Trio, a Rho Family GEF, Interacts with the Presynaptic Active Zone Proteins Piccolo and Bassoon|journal=PLOS ONE|volume=11|issue=12|pages=e0167535|doi=10.1371/journal.pone.0167535|pmc=5132261|pmid=27907191|bibcode=2016PLoSO..1167535T |doi-access=free}} DAAM1,{{Cite journal|last1=Wagh|first1=Dhananjay|last2=Terry-Lorenzo|first2=Ryan|last3=Waites|first3=Clarissa L.|last4=Leal-Ortiz|first4=Sergio A.|last5=Maas|first5=Christoph|last6=Reimer|first6=Richard J.|last7=Garner|first7=Craig C.|date=2015-01-01|title=Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1|journal=PLOS ONE|volume=10|issue=4|pages=e0120093|doi=10.1371/journal.pone.0120093|pmc=4405365|pmid=25897839|bibcode=2015PLoSO..1020093W |doi-access=free}} and Profilin.{{Cite journal|last1=Wang|first1=X.|last2=Kibschull|first2=M.|last3=Laue|first3=M. M.|last4=Lichte|first4=B.|last5=Petrasch-Parwez|first5=E.|last6=Kilimann|first6=M. W.|date=1999-10-04|title=Aczonin, a 550-kD putative scaffolding protein of presynaptic active zones, shares homology regions with Rim and Bassoon and binds profilin|journal=The Journal of Cell Biology|volume=147|issue=1|pages=151–162|pmc=2164979|pmid=10508862|doi=10.1083/jcb.147.1.151}}
Clinical relevance
Recurrent mutations in this gene have been associated to cases of diffuse large B-cell lymphoma.{{cite journal | vauthors = Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, Cruz-Gordillo P, Knoechel B, Asmann YW, Slager SL, Novak AJ, Dogan A, Ansell SM, Link BK, Zou L, Gould J, Saksena G, Stransky N, Rangel-Escareño C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Hernández-Lemus E, Schwarz-Cruz y Celis A, Imaz-Rosshandler I, Ojesina AI, Jung J, Pedamallu CS, Lander ES, Habermann TM, Cerhan JR, Shipp MA, Getz G, Golub TR | title = Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 10 | pages = 3879–84 | date = Mar 2012 | pmid = 22343534 | pmc = 3309757 | doi = 10.1073/pnas.1121343109 | bibcode = 2012PNAS..109.3879L | doi-access = free }} Recent evidence has shown that a homozygous, nonsense PCLO mutation is the genetic cause of the autosomal recessive neurodegenerative disorder, pontocerebellar hypoplasia type III (PCH3).{{Cite journal|last1=Ahmed|first1=Mustafa Y.|last2=Chioza|first2=Barry A.|last3=Rajab|first3=Anna|last4=Schmitz-Abe|first4=Klaus|last5=Al-Khayat|first5=Aisha|last6=Al-Turki|first6=Saeed|last7=Baple|first7=Emma L.|last8=Patton|first8=Michael A.|last9=Al-Memar|first9=Ali Y.|date=2015-04-28|title=Loss of PCLO function underlies pontocerebellar hypoplasia type III|journal=Neurology|language=en|volume=84|issue=17|pages=1745–1750|doi=10.1212/WNL.0000000000001523|pmc=4424132|pmid=25832664}}
References
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Further reading
{{refbegin | 2}}
- {{cite journal | title = Toward a complete human genome sequence | journal = Genome Research | volume = 8 | issue = 11 | pages = 1097–108 | date = Nov 1998 | pmid = 9847074 | doi = 10.1101/gr.8.11.1097 | last1 = Sanger Centre | first1 = The | last2 = Washington University Genome Sequencing Cente | first2 = The | doi-access = free }}
- {{cite journal | vauthors = Wang X, Kibschull M, Laue MM, Lichte B, Petrasch-Parwez E, Kilimann MW | title = Aczonin, a 550-kD putative scaffolding protein of presynaptic active zones, shares homology regions with Rim and Bassoon and binds profilin | journal = The Journal of Cell Biology | volume = 147 | issue = 1 | pages = 151–62 | date = Oct 1999 | pmid = 10508862 | pmc = 2164979 | doi = 10.1083/jcb.147.1.151 }}
- {{cite journal | vauthors = Fenster SD, Chung WJ, Zhai R, Cases-Langhoff C, Voss B, Garner AM, Kaempf U, Kindler S, Gundelfinger ED, Garner CC | title = Piccolo, a presynaptic zinc finger protein structurally related to bassoon | journal = Neuron | volume = 25 | issue = 1 | pages = 203–14 | date = Jan 2000 | pmid = 10707984 | doi = 10.1016/S0896-6273(00)80883-1 | s2cid = 10177138 | doi-access = free }}
- {{cite journal | vauthors = Fenster SD, Garner CC | title = Gene structure and genetic localization of the PCLO gene encoding the presynaptic active zone protein Piccolo | journal = International Journal of Developmental Neuroscience | volume = 20 | issue = 3–5 | pages = 161–71 | year = 2002 | pmid = 12175852 | doi = 10.1016/S0736-5748(02)00046-1 | s2cid = 21515091 }}
- {{cite journal | vauthors = Takao-Rikitsu E, Mochida S, Inoue E, Deguchi-Tawarada M, Inoue M, Ohtsuka T, Takai Y | title = Physical and functional interaction of the active zone proteins, CAST, RIM1, and Bassoon, in neurotransmitter release | journal = The Journal of Cell Biology | volume = 164 | issue = 2 | pages = 301–11 | date = Jan 2004 | pmid = 14734538 | pmc = 2172332 | doi = 10.1083/jcb.200307101 }}
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External links
- {{PDBe-KB2|Q9Y6V0|Protein piccolo}}
{{gene-7-stub}}