Flamingo is a member of the adhesion-GPCR family of protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s. Flamingo has sequence homology to cadherin

Cadherin

Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...

s and G protein-coupled receptor

G protein-coupled receptor

G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

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

Drosophila

Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...

protein involved in planar cell polarity. Mammals have three flamingo homologs, CELSR1

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 :...

, CELSR2

CELSR2

Cadherin EGF LAG seven-pass G-type receptor 2 is a protein that in humans is encoded by the CELSR2 gene.-Further reading:...

, CELSR3

CELSR3

Cadherin EGF LAG seven-pass G-type receptor 3 is a protein that in humans is encoded by the CELSR3 gene.- Further reading :...

. 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

Epidermal growth factor

Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR...

-like, Laminin G-like and Cadherin

Cadherin

Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...

-like sequences in its N-terminal extracellular domain.

Function in dendrite morphology

In Drosophila, flamingo mutants were found to have abnormal dendrite

Dendrite

Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...

 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

RNAI

RNAI is a non-coding RNA that is an antisense repressor of the replication of some E. coli plasmids, including ColE1. Plasmid replication is usually initiated by RNAII, which acts as a primer by binding to its template DNA. The complementary RNAI binds RNAII prohibiting it from its initiation role...

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

Cerebral cortex

The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...

 cultures and Purkinje neurons in cerebellar

Cerebellum

The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...

 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 cell

Hair cell

Hair cells are the sensory receptors of both the auditory system and the vestibular system in all vertebrates. In mammals, the auditory hair cells are located within the organ of Corti on a thin basilar membrane in the cochlea of the inner ear...

s of the mouse inner ear.