Accelerator and Brake Proteins Control Melanin Production

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By Michelle Mukonyora

2 June 2016

Melanin is more than the pigment that is responsible for our diverse skin, hair and eye colours. It helps protect the DNA in our skin and eyes from damage by the sun’s UV rays. People who do not produce enough melanin suffer from disorders such as albinism, vitiligo, as well as susceptibility to cancers of the skin and eyes. If we figure out how melanin production is controlled, we can then begin to find ways to treat melanin production disorders.

Image credit: http://www.buzzle.com/articles/what-causes-albinism.html

Melanosomes are the melanin producing factories found inside melanin producing cells. They comprise small compartments encapsulated by a membrane (Figure 1).

Figure 1: Melanosomes are small cellular compartments in which melanin is produced (orange circles)
Scientists at Brown University recently discovered a protein called TPC2 that slows down melanin production. TPC2 is located on the melanosome membrane, and it is a special type of protein known as an ‘ion channel’. Channels act as ports of entry by controlling what goes in and out of membrane bound compartments. In this instance, TPC2 controls the movement of positively charged sodium ions (Na+) out of the melanosome. As the concentration of Na+ decreases inside the melanosomes, the acidity increases. It is this high acidity, which halts the activity of the enzymes responsible for melanin production. ​
​Almost two years ago, the same research group headed by Elena Oancea, discovered another ion channel called OCA2, which when mutated, is implicated in a type of albinism. This was the first time that an ion channel on a melanosome was characterized. A normally functioning OCA2 ion channel is responsible for increasing the rate of melanin production. It does the opposite action of TPC2 by decreasing the pH. OCA2 decreases the pH by pumping negatively charged chloride ions (Cl-) out of melanosomes. OCA2 and TPC2 therefore act in tandem as an accelerator and brake to maintain a balance of melanin production.

Now that the role of TPC2 is known, we can figure out what mutations cause it to malfunction. This is the first step in finding ways to treat TPC2-related disorders. Controlling the activity of TPC2 may prove to be tricky because it also controls ion movements across other important membranes in the cell. A possible way of circumventing this would be through the targeted delivery of drug molecules to melanosomes.

Read more: Bellono, N. W et al. (2014) An intracellular anion channel critical for pigmentation. eLife3:e04543. doi:10.7554/eLife.04543.018