Feb. 27, 2008 Skin color is one of the most visible indicators that helps distinguish human appearance, and a new study provides more detail as to how one protein helps produce this wide palette.
In 2005 researchers identified a gene called SLC24A5 as a key determinant of skin color. Rebecca Ginger and colleagues now confirm that the protein product of this gene (NCKX5) is an ion exchanger; it exchanges sodium for calcium across a membrane, regulated by potassium. But unlike other NCKX proteins, they found that NCKX5 is not present on the cell surface, but internally in a compartment known as the trans-Golgi network. This compartment is where new proteins and vesicles are processed, modified and sorted.
When the researchers knocked out NCKX5 in melanocytes (the skin cells that manufacture the melanin pigment), melanin production decreased dramatically. They also demonstrated that changing the ancestral amino acid (alanine) at position 111 to the European form associated with lighter skintone (threonine) reduced NCKX5's exchanger activity.
While they plan on teasing out the exact biological mechanism, Ginger and colleagues propose that NCKX5 could play a direct role in the trafficking decisions that influence the assembly of melanosomes, the specialized cell vesicles where melanin is produced. Alterations that increase or decrease NCKX5 effectiveness would be expected to influence total skin pigment production.
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