Flamingo is a member of the adhesion-GPCR family of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s. Flamingo has sequence homology to cadherins and

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

s (GPCR). Flamingo was originally identified as a ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...

'' protein involved in

planar cell polarity Planar Cell Polarity (PCP) is the protein mediated signaling that coordinates the orientation of cells in a layer of epithelial tissue. In vertebrates, examples of mature PCP oriented tissue are the stereo-cilia bundles in the inner ear, motile cil ...

. Mammals have three flamingo homologs,

CELSR1 Cadherin EGF LAG seven-pass G-type receptor 1 also known as flamingo homolog 2 or cadherin family member 9 is a protein that in humans is encoded by the ''CELSR1'' gene. Function The protein encoded by this gene is a member of the flamingo su ...

, CELSR2,

CELSR3 Cadherin EGF LAG seven-pass G-type receptor 3 is a protein that in humans is encoded by the ''CELSR3'' gene. The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consist ...

. 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.

Axon fascicles

Mice that lack CELSR3 have altered bundling of

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...

s to form fascicles.

Function in dendrite morphology

In ''Drosophila'', flamingo mutants were found to have abnormal

dendrite Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the ...

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 RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...

was used to alter CELSR2 expression in cortical and cerebral brain slice cultures. The dendrites of

pyramidal neuron Pyramidal cells, or pyramidal neurons, are a type of multipolar neuron found in areas of the brain including the cerebral cortex, the hippocampus, and the amygdala. Pyramidal neurons are the primary excitation units of the mammalian prefrontal cor ...

s in cortical cultures and Purkinje cells, Purkinje neurons in cerebellum, cerebellar cultures were simplified when CELSR2 expression was reduced.

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.

References

{{DEFAULTSORT:Flamingo (Protein) Adhesion G protein-coupled receptors G protein-coupled receptors