CX3C motif chemokine receptor 1

[5][6][7] As the name suggests, this receptor binds the inflammatory chemokine CX3CL1 (also called neurotactin in mice or fractalkine in humans).

Interaction of CX3CR1 with CX3CL1 can mediate migration, adhesion and retention of leukocytes, because Fractalkine exists as membrane-anchored protein (mCX3CL1) as well as cleaved soluble molecule (sCX3CL1) due to proteolysis by metalloproteinases (MPPs).

The shedded form carries out typical function of conventional chemokines, the chemotaxis, while the membrane-bound protein behaves as adhesion molecule for facilitation of diapedesis.

Moreover, their distinct cell expression is dependent on specific tissues and organs, which provides broad sphere of biological activity.

[10][11] Two missense mutations in CX3CR1 gene, variants of single nucleotide polymorphism (SNP) of the receptor, are responsible for functional change of the protein.

[12][13][14] Orthologs of CX3CR1 gene are found among animals, especially in mammals with high functional similarity, namely chimpanzee, dog, cat, mouse and rat.

[20] Communication in blood vessels through the CX3CL1-CX3CR1 axis between endothelial cells and monocytes is responsible for formation of extracellular matrix and angiogenesis.

[21] CX3CR1 is integral membrane protein formed by 355 amino acids with molecular weight around 40 kDa, which consist of three distinguishable segments: extracellular, transmembrane and intracellular part.

This family is also known as T-transmembrane receptors (7-TM) by reason of 7 α-helices of transmembrane protein, which are alternately located in the cell's cytoplasmic membrane.

It is followed by conformational change and component's dissociation of the heterotrimeric G complex, which consists of three subunits: α (alpha), β (beta) and γ (gamma).

[10][24] Moreover, CX3CR1 variants have been described to modify the survival time and the progression rate of patients with amyotrophic lateral sclerosis.

[27] As mentioned before, this receptor and its ligand are important for the metabolism of the bone tissue in terms of differentiation of osteoclasts and osteoblasts.