Flamingo (protein)
{{Short description|Protein}}
{{Infobox protein
| Name = cadherin, EGF LAG seven-pass G-type receptor 1 (flamingo homolog, Drosophila)
| Symbol = CELSR1 | EntrezGene = 9620 | OMIM = 604523
}}
{{Infobox protein
| Name = cadherin, EGF LAG seven-pass G-type receptor 2 (flamingo homolog, Drosophila)
| Symbol = CELSR2 | AltSymbols = EGFL2 | EntrezGene = 1952 | OMIM = 604265
}}
{{Infobox protein
| Name =cadherin, EGF LAG seven-pass G-type receptor 3 (flamingo homolog, Drosophila)
| Symbol = CELSR3 | AltSymbols = EGFL1 | EntrezGene = 1951 | OMIM = 604264
}}
Flamingo is a member of the adhesion-GPCR family of proteins. Flamingo has sequence homology to cadherins and G protein-coupled receptors (GPCR). Flamingo was originally identified as a Drosophila protein involved in planar cell polarity.{{cite journal |doi=10.1016/S0092-8674(00)80046-X |vauthors=Usui T, Shima Y, Shimada Y |title=Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled |journal=Cell |volume=98 |issue=5 |pages=585–95 |date=September 1999 |pmid=10490098 |display-authors=etal|doi-access=free }} Mammals have three flamingo homologs, CELSR1, CELSR2, CELSR3. In mice, all three have distinct expression patterns in organs such as the kidney, skin, and lungs, as well as the brain.{{cite journal |doi=10.1016/S0925-4773(01)00623-2 |vauthors=Tissir F, De-Backer O, Goffinet AM, Lambert de Rouvroit C |title=Developmental expression profiles of Celsr (Flamingo) genes in the mouse |journal=Mech. Dev. |volume=112 |issue=1–2 |pages=157–60 |date=March 2002 |pmid=11850187 |doi-access=free }}
Protein structure
Flamingo is an atypical cadherin, with a cadherin-like extracellular domain, composed of cadherin and EGF adhesive repeats, that can bind to other Flamingo proteins expressed on neighboring cells. The transmembrane domain, however, is a 7-pass membrane domain most structurally similar to that of a G protein-coupled receptor, though it is not known to interact with G protein.{{Cite journal |last=Goffinet |first=Andre M. |last2=Tissir |first2=Fadel |date=2017-09-01 |title=Seven pass Cadherins CELSR1-3 |url= |journal=Seminars in Cell & Developmental Biology |series=Spectraplakins, versatile roles in physiology and pathology |volume=69 |pages=102–110 |doi=10.1016/j.semcdb.2017.07.014 |issn=1084-9521|hdl=2078.1/191623 |hdl-access=free }}
Planar cell polarity
Flamingo is one of the core proteins in the planar cell polarity (PCP) pathway, which is required for successful body elongation during gastrulation in early development, as well as the formation of developing organs such as the brain, inner ear, and kidney. It has been extensively studied for its role in patterning developmental tissues in a wide range of species.{{Cite journal |last=Butler |first=Mitchell T. |last2=Wallingford |first2=John B. |date=June 2017 |title=Planar cell polarity in development and disease |url=https://www.nature.com/articles/nrm.2017.11 |journal=Nature Reviews Molecular Cell Biology |language=en |volume=18 |issue=6 |pages=375–388 |doi=10.1038/nrm.2017.11 |issn=1471-0072 |pmc=5826606 |pmid=28293032}} CELSR1 is the primary flamingo homolog involved in PCP in vertebrates.{{cite journal |display-authors=etal |vauthors=Curtin JA, Quint E, Tsipouri V |date=July 2003 |title=Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse |journal=Curr. Biol. |volume=13 |issue=13 |pages=1129–33 |doi=10.1016/S0960-9822(03)00374-9 |pmid=12842012 |doi-access=free}} In humans, CELSR1 mutations are correlated with severe birth defects, including brain, hearing, and kidney defects, due to incorrect establishment of planar polarity in those organs.{{Cite journal |last=Robinson |first=Alexis |last2=Escuin |first2=Sarah |last3=Doudney |first3=Kit |last4=Vekemans |first4=Michel |last5=Stevenson |first5=Roger E. |last6=Greene |first6=Nicholas D.E. |last7=Copp |first7=Andrew J. |last8=Stanier |first8=Philip |date=February 2012 |title=Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis |url=|journal=Human Mutation |language=en |volume=33 |issue=2 |pages=440–447 |doi=10.1002/humu.21662 |pmc=4772123 |pmid=22095531}}{{Cite journal |last=Brzóska |first=Hortensja Ł. |last2=d’Esposito |first2=Angela M. |last3=Kolatsi-Joannou |first3=Maria |last4=Patel |first4=Vishal |last5=Igarashi |first5=Peter |last6=Lei |first6=Yunping |last7=Finnell |first7=Richard H. |last8=Lythgoe |first8=Mark F. |last9=Woolf |first9=Adrian S. |last10=Papakrivopoulou |first10=Eugenia |last11=Long |first11=David A. |date=December 2016 |title=Planar cell polarity genes Celsr1 and Vangl2 are necessary for kidney growth, differentiation, and rostrocaudal patterning |url=|journal=Kidney International |volume=90 |issue=6 |pages=1274–1284 |doi=10.1016/j.kint.2016.07.011 |issn=0085-2538 |pmc=5126096 |pmid=27597235}}
Function in neurons
In Drosophila, flamingo mutants were found to have abnormal dendrite branching, outgrowth and routing.{{cite journal |doi=10.1101/gad.13.19.2549 |vauthors=Gao FB, Brenman JE, Jan LY, Jan YN |title=Genes regulating dendritic outgrowth, branching, and routing in Drosophila |journal=Genes Dev. |volume=13 |issue=19 |pages=2549–61 |date=October 1999 |pmid=10521399 |pmc=317067 }} Kimura et al. proposed that flamingo regulates dendrite branch elongation and prevents the dendritic trees of adjacent Drosophila sensory neurons from having overlap of dendritic arbors.{{cite journal |vauthors=Kimura H, Usui T, Tsubouchi A, Uemura T |title=Potential dual molecular interaction of the Drosophila 7-pass transmembrane cadherin Flamingo in dendritic morphogenesis |journal=J. Cell Sci. |volume=119 |issue=Pt 6 |pages=1118–29 |date=March 2006 |pmid=16507587 |doi=10.1242/jcs.02832 |doi-access=free }}
A study of mammalian flamingo homolog CELSR2 found that it is involved in the regulation of dendrite growth. RNAi was used to alter CELSR2 expression in cortical and cerebral brain slice cultures. The dendrites of pyramidal neurons in cortical cultures and Purkinje neurons in cerebellar cultures were simplified when CELSR2 expression was reduced.{{cite journal |vauthors=Shima Y, Kengaku M, Hirano T, Takeichi M, Uemura T |title=Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin |journal=Dev. Cell |volume=7 |issue=2 |pages=205–16 |date=August 2004 |pmid=15296717 |doi=10.1016/j.devcel.2004.07.007 |doi-access=free }} Mice that lack CELSR3 have altered bundling of axons to form fascicles.{{cite journal |vauthors=Tissir F, Bar I, Jossin Y, De Backer O, Goffinet AM |date=April 2005 |title=Protocadherin Celsr3 is crucial in axonal tract development |journal=Nat. Neurosci. |volume=8 |issue=4 |pages=451–7 |doi=10.1038/nn1428 |pmid=15778712}}
References
{{reflist}}
{{G protein-coupled receptors}}
{{DEFAULTSORT:Flamingo (Protein)}}