Flamingo (protein)

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cadherin, EGF LAG seven-pass G-type receptor 1 (flamingo homolog, Drosophila)
Identifiers
Symbol CELSR1
Entrez 9620
OMIM 604523
cadherin, EGF LAG seven-pass G-type receptor 2 (flamingo homolog, Drosophila)
Identifiers
Symbol CELSR2
Alt. symbols EGFL2
Entrez 1952
OMIM 604265
cadherin, EGF LAG seven-pass G-type receptor 3 (flamingo homolog, Drosophila)
Identifiers
Symbol CELSR3
Alt. symbols EGFL1
Entrez 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.[1] Mammals have three flamingo homologs, CELSR1, CELSR2, CELSR3. In mice all three have distinct expression patterns in the brain.[2]

Adhesion G protein coupled receptors[edit]

The adhesion-GPCR family has over thirty members in the human genome.[3] The adhesion GPCRs are seven transmembrane helix proteins that have long N-terminal domains. For example, flamingo has EGF-like, Laminin G-like and Cadherin-like sequences in its N-terminal extracellular domain.

Axon fascicles[edit]

Mice that lack CELSR3 have altered bundeling of axons to form fascicles.[4]

Function in dendrite morphology[edit]

In Drosophila, flamingo mutants were found to have abnormal dendrite branching, outgrowth and routing.[5] 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.[6]

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.[7]

Vertebrate planar cell polarity[edit]

CELSR1 was shown to be required for the normal polarized position of kinocilia to one side of hair cells of the mouse inner ear.[8]

References[edit]

  1. ^ Usui T, Shima Y, Shimada Y, et al. (September 1999). "Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled". Cell 98 (5): 585–95. doi:10.1016/S0092-8674(00)80046-X. PMID 10490098. 
  2. ^ Tissir F, De-Backer O, Goffinet AM, Lambert de Rouvroit C (March 2002). "Developmental expression profiles of Celsr (Flamingo) genes in the mouse". Mech. Dev. 112 (1-2): 157–60. doi:10.1016/S0925-4773(01)00623-2. PMID 11850187. 
  3. ^ Bjarnadóttir TK, Fredriksson R, Höglund PJ, Gloriam DE, Lagerström MC, Schiöth HB (July 2004). "The human and mouse repertoire of the adhesion family of G-protein-coupled receptors". Genomics 84 (1): 23–33. doi:10.1016/j.ygeno.2003.12.004. PMID 15203201. 
  4. ^ Tissir F, Bar I, Jossin Y, De Backer O, Goffinet AM (April 2005). "Protocadherin Celsr3 is crucial in axonal tract development". Nat. Neurosci. 8 (4): 451–7. doi:10.1038/nn1428. PMID 15778712. 
  5. ^ Gao FB, Brenman JE, Jan LY, Jan YN (October 1999). "Genes regulating dendritic outgrowth, branching, and routing in Drosophila". Genes Dev. 13 (19): 2549–61. doi:10.1101/gad.13.19.2549. PMC 317067. PMID 10521399. 
  6. ^ Kimura H, Usui T, Tsubouchi A, Uemura T (March 2006). "Potential dual molecular interaction of the Drosophila 7-pass transmembrane cadherin Flamingo in dendritic morphogenesis". J. Cell. Sci. 119 (Pt 6): 1118–29. doi:10.1242/jcs.02832. PMID 16507587. 
  7. ^ Shima Y, Kengaku M, Hirano T, Takeichi M, Uemura T (August 2004). "Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin". Dev. Cell 7 (2): 205–16. doi:10.1016/j.devcel.2004.07.007. PMID 15296717. 
  8. ^ Curtin JA, Quint E, Tsipouri V, et al. (July 2003). "Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse". Curr. Biol. 13 (13): 1129–33. doi:10.1016/S0960-9822(03)00374-9. PMID 12842012.