Biology:Flamingo (protein)

From HandWiki
cadherin, EGF LAG seven-pass G-type receptor 1 (flamingo homolog, Drosophila)
Identifiers
SymbolCELSR1
NCBI gene9620
OMIM604523
cadherin, EGF LAG seven-pass G-type receptor 2 (flamingo homolog, Drosophila)
Identifiers
SymbolCELSR2
Alt. symbolsEGFL2
NCBI gene1952
OMIM604265
cadherin, EGF LAG seven-pass G-type receptor 3 (flamingo homolog, Drosophila)
Identifiers
SymbolCELSR3
Alt. symbolsEGFL1
NCBI gene1951
OMIM604264

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

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

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

Function in dendrite morphology

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

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

  1. "Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled". Cell 98 (5): 585–95. September 1999. doi:10.1016/S0092-8674(00)80046-X. PMID 10490098. 
  2. "Developmental expression profiles of Celsr (Flamingo) genes in the mouse". Mech. Dev. 112 (1–2): 157–60. March 2002. doi:10.1016/S0925-4773(01)00623-2. PMID 11850187. 
  3. "The human and mouse repertoire of the adhesion family of G-protein-coupled receptors". Genomics 84 (1): 23–33. July 2004. doi:10.1016/j.ygeno.2003.12.004. PMID 15203201. 
  4. "Protocadherin Celsr3 is crucial in axonal tract development". Nat. Neurosci. 8 (4): 451–7. April 2005. doi:10.1038/nn1428. PMID 15778712. 
  5. "Genes regulating dendritic outgrowth, branching, and routing in Drosophila". Genes Dev. 13 (19): 2549–61. October 1999. doi:10.1101/gad.13.19.2549. PMID 10521399. 
  6. "Potential dual molecular interaction of the Drosophila 7-pass transmembrane cadherin Flamingo in dendritic morphogenesis". J. Cell Sci. 119 (Pt 6): 1118–29. March 2006. doi:10.1242/jcs.02832. PMID 16507587. 
  7. "Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin". Dev. Cell 7 (2): 205–16. August 2004. doi:10.1016/j.devcel.2004.07.007. PMID 15296717. 
  8. "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. July 2003. doi:10.1016/S0960-9822(03)00374-9. PMID 12842012.