- Flamingo (protein)
Flamingo is a member of the adhesion-GPCR family of
protein s. Flamingo has sequence homology tocadherin s andG protein-coupled receptor s (GPCR). Flamingo was originally identified as a "Drosophila " protein involved in planar cell polarity. [T. Usui, Y. Shima, Y. Shimada, S. Hirano, R. Burgess, T. Schwarz, M. Takeichi and T. Uemura (1999) "Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled" in "Cell" Volume 98, pages 585-595. Entrez Pubmed|10490098] Mammals have three flamingo homologs,CELSR1 ,CELSR2 ,CELSR3 . In mice all three have distinct expression patterns in the brain. [F. Tissir, O. De-Backer, A. Goffinet and C. Lambert de Rouvroit C (2002) "Developmental expression profiles of Celsr (Flamingo) genes in the mouse" in "Mechanisms of development" Volume 112, pages 157-160. Entrez Pubmed|11850187]Adhesion G protein coupled receptors
The adhesion-GPCR family has over thirty members in the human genome. [T. Bjarnadóttir, R. Fredriksson, P. Höglund, D. Gloriam, M. Lagerström and H. Schiöth (2004) "The human and mouse repertoire of the adhesion family of G-protein-coupled receptors" in "Genomics" Volume 84, pages 23-33. Entrez Pubmed|15203201] The adhesion GPCRs are seven transmembrane helix proteins that have long N-terminal domains. For example, flamingo has EGF-like,
Laminin G -like andCadherin -like sequences in its N-terminal extracellular domain.Axon fascicles
Mice that lack CELSR3 have altered bundeling of
axon s to form fascicles. [F. Tissir, I. Bar, Y. Jossin, O. De Backer and A. Goffinet (2005) "Protocadherin Celsr3 is crucial in axonal tract development." in "Nature Neuroscience" Volume 8, pages 451-457. Entrez Pubmed|15778712]Function in dendrite morphology
In "Drosophila", flamingo mutants were found to have abnormal
dendrite branching, outgrowth and routing. [Fen-Biao Gao, Jay E. Brenman, Lily Yeh Jan and Yuh Nung Jan (1999) "Genes regulating dendritic outgrowth, branching, and routing in Drosophila" in Genes Dev Volume 13, pages 2549-61. Entrez Pubmed|10521399] 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. [H. Kimura, T. Usui, A. Tsubouchi and T. Uemura (2006) "Potential dual molecular interaction of the Drosophila 7-pass transmembrane cadherin Flamingo in dendritic morphogenesis" in "Journal of Cell Science" Volume 119, pages 1118-1129. Entrez Pubmed|16507587]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 ofpyramidal neuron s in cortical cultures and Purkinjeneurons in cerebellar cultures were simplified when CELSR2 expression was reduced. [Y. Shima, M. Kengaku, T. Hirano, M. Takeichi and T. Uemura (2004) "Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin" in Developmental cell Volume 7, pages 205-16. Entrez Pubmed|15296717]Vertebrate planar cell polarity
CELSR1 was shown to be required for the normal polarized position of
kinocilia to one side ofhair cell s of the mouse inner ear. [J. Curtin, E. Quint, V. Tsipouri, R. Arkell, B. Cattanach, A. Copp, D. Henderson, N. Spurr, P. Stanier, E. Fisher, P. Nolan, K. Steel, S. Brown, I. Gray and J. Murdoch (2003) "Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse" in Current biology Volume 13, pages 1129-1133. Entrez PubMed 12842012]References
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