cadherin, EGF LAG seven-pass G-type receptor 3 (flamingo homolog, Drosophila)
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.
Function in dendrite morphology
cadherin, EGF LAG seven-pass G-type receptor 2 (flamingo homolog, Drosophila)
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.
cadherin, EGF LAG seven-pass G-type receptor 1 (flamingo homolog, Drosophila)
Vertebrate 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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