Fractalkine (CX3CL1)

Fractalkine (CX3CL1)

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About Fractalkine:

CX3CL1 is more commonly known as fractalkine. In fact, the reason it often goes by the other name is because the gene that encodes fractalkine is CX3CL1. It is a protein that’s present in the human body and is often referred to as being a chemokine ligand 1 protein. You’ll find it along the human chromosome 16, where it shares this location with many other CC chemokines (notably; CCL17 and CCL22).

CX3CL1 is a big protein, in comparison to many other proteins in the human body. It contains a large number of amino acids - 373 to be precise - and is the owner of many different domains. As of right now, it’s the sole member of a chemokine family called the CXsC family.
The reason it forms its own chemokine family is that it doesn’t follow the typical structural traits of other chemokines in humans. More specifically, it has a different polypeptide structure, which isn’t found anywhere else. Research has concluded that there is a difference in how the N-terminal cysteines are spaced in CX3CL1 compared to the CC and CXC chemokine families. In CX3CL1 you will find three amino acids that break up the first pair of cysteines in the protein cell. Comparatively, there are no amino acids separating the initial pair of cysteines in CC chemokines, and there is a sole amino acid in CXC chemokines.
As mentioned, this is a very long protein with 373 amino acids present, and it has a chemokine domain on the top of a mucin-like stalk that extends outwards from the cell.

Mechanism & Interactions
Thanks to its mucin-like stalk, CX3CL1 has the ability to bind to different cells on their surface. This makes it a cell-binding chemokine, and it is largely produced in endothelial cells. Similarly, when this chemokine binds to the surface of cells, it helps encourage leukocytes to fix themselves to the endothelial cells.
However, as well as the cell-binding version of CX3CL1, a soluble version has also been discovered by researchers. Various tests have found that this version of the chemokine is excellent at attracting both monocytes and T cells to the area it’s present in.
For any of this to happen, CX3CL1 needs to interact with a chemokine receptor. As a consequence, it binds with the receptor CX3CR1. You’ll find CX3CL1 - or fractalkine - in many areas of the body, most notably the brain. Neural cells are especially abundant in fractalkine, and you will commonly find the CX3CR1 receptor on microglial cells.

The primary functions of CX3CL1 are to help attract and fix different cells. The soluble version helps in the attraction of T cells and monocytes, with the cell-bound version working on fixing leukocytes. Following on from this, it has also been linked to cell migration. Mainly, CX3CL1 is suggested to be absolutely paramount for microglial cell migration.
Furthermore, this chemokine is highly abundant in the hippocampus part of the brain and has been found to help with the regulation of glutamate-mediated neurotransmission tone. This means that CX3CL1 could also function as part of the synaptic scaling process.