Cell Biology

In our previous module, we discussed the correlation between the cysteine amino acid substitution within the MC1R protein and lighter fur color within mice. But why exactly does this single amino acid substitution, the effect of a single nucleotide substitution, cause such a drastic phenotypic response such as fur color lightening? 

The MC1R gene, as previously discussed, codes for the MC1R protein. This MC1R protein is a transmembrane protein.

Transmembrane Proteins

Transmembrane proteins are proteins that are able to wedge into the membrane of a cell, and are capable of many different functions. Ranging from acting as a channel into or out of the cell, to acting as a receptor for certain hormones and stimulating proteins, the main responsibility of transmembrane proteins is to be able to communicate with the environment outside of the cell.

In the case of the MC1R transmembrane protein, one of its proper functions, once inserted into the cell membrane, is to bind with a hormone, known as the Melanocyte stimulating hormone, or MSH. The binding of MSH upon the MC1R transmembrane protein causes the MC1R protein to change its shape, which then allows it to initiate a series of reactions within the cell. This ultimately produces eumelanin, the pigment responsible for the dark color found in hair and fur.

Melanocytes are located at the base of the hair papilla and produce a pigment molecule called eumelanin. Pigment is then transported from the base to the hair cortex where coloration becomes visible.

The Eumelanin Pigment

Eumelanin is a polymer of cross-linked dihydroxyindole carboxylic acids. It is composed of many units that can vary slightly in their composition.

The differences in mouse fur color are best described by examining melanocyte cell function. Melanocytes are located at the base of the hair papilla and make a pigment molecule called eumelanin. Pigment is then transported from the base to the hair cortex where coloration becomes visible.

Protein & Function

Within the wild type version of the MC1R gene, this process occurs as normal; the MC1R gene is transcribed into mRNA, then translated into a transmembrane protein, which in turn is inserted into the membrane of the cell. Once present in the cell, it can readily react with MSH, which alters the shape of the MC1R protein, which in turn allows it to react and ultimately produce eumelanin, the pigment that darkens mouse fur color. 

However, the mutant version of the MC1R gene, nucleotide 199 is substituted with a thymine, and thus the following amino acid at position 67 is substituted with a cysteine. This single amino acid substitution changes the ability of the protein; it is unable to change its shape as it normally can, which inhibits its ability to initiate the biochemical reactions necessary to eventually produce the eumelanin pigment responsible for darker fur color in mice.