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 neurons
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
in
cerebellar
The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...
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
A kinocilium is a special type of cilium on the apex of hair cells located in the sensory epithelium of the vertebrate inner ear.
Anatomy in humans
Kinocilia are found on the apical surface of hair cells and are involved in both the morphogenesis ...
to one side of
hair cell
Hair cells are the sensory receptors of both the auditory system and the vestibular system in the ears of all vertebrates, and in the lateral line organ of fishes. Through mechanotransduction, hair cells detect movement in their environment. ...
s of the mouse inner ear.
References
{{DEFAULTSORT:Flamingo (Protein)
Adhesion G protein-coupled receptors
G protein-coupled receptors