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. Mammals have three flamingo homologs, CELSR1, CELSR2, CELSR3. In mice all three have distinct expression patterns in the brain.
Adhesion G protein coupled receptors
The adhesion-GPCR family has over thirty members in the human genome. 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.
Mice that lack CELSR3 have altered bundeling of axons to form fascicles.
Function in dendrite morphology
Template:ProteinShort In Drosophila, flamingo mutants were found to have abnormal dendrite branching, outgrowth and routing. 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.
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. Template:ProteinShort
Vertebrate planar cell polarity
CELSR1 was shown to be required for the normal polarized position of kinocilia to one side of hair cells of the mouse inner ear.
- ↑ 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. Template:Entrez Pubmed
- ↑ 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. Template:Entrez Pubmed
- ↑ 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. Template:Entrez Pubmed
- ↑ 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. Template:Entrez Pubmed
- ↑ 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. Template:Entrez Pubmed
- ↑ 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. Template:Entrez Pubmed
- ↑ 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. Template:Entrez Pubmed
- ↑ 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