Skin Sees the Light with Rhodopsin

Science Signaling  29 Nov 2011:
Vol. 4, Issue 201, pp. ec331
DOI: 10.1126/scisignal.4201ec331

Melanocytes in human skin exhibit temporally distinct responses to ultraviolet radiation (UVR): Ultraviolet B (UVB) triggers a delayed pigmentation response due to DNA damage that activates a genetic pathway involved in melanin production, whereas UVA triggers an immediate pigmentation response through an unknown mechanism. Wicks et al. examined Ca2+ transients in primary human epidermal melanocytes in response to UVR (90% UVA, 10% UVB) or to UVA or UVB specifically and found a retinal-dependent signal, which did not require extracellular Ca2+ and was blocked by depletion of internal Ca2+ stores. Exposure of the cells to a heterotrimeric G protein inhibitor or an inhibitor of phospholipase C blocked the UVR-mediated Ca2+ transients, suggesting the involvement of a G protein–coupled receptor (GPCR). Transcript analysis (by reverse transcriptase polymerase chain reaction) and protein analysis (by Western blotting) showed that the light-responsive, retinal-binding GPCR rhodopsin (best known for its role in vision) was present in the melanocytes. Knockdown of rhodopsin reduced the UVR-induced Ca2+ transients and exclusion of retinal inhibited rapid melanin production induced by UVR. Although UVA, not UVB, was most effective in promoting the Ca2+ transients and the rapid melanin production, the spectral profile of the response in melanocytes differed from that measured in other systems for rhodopsin. The authors speculate that the cellular environment of melanocytes may stabilize the meta II–like state of rhodopsin, which responds to the spectrum that produces the rapid Ca2+ and melanin response, or rhodopsin may interact with another GPCR or form a heterodimer with another protein that alters its light sensitivity.

N. L. Wicks, J. W. Chan, J. A. Najera, J. M. Ciriello, E. Oancea, UVA phototransduction drives early melanin synthesis in human melanocytes. Curr. Biol. 21, 1906–1911 (2011). [Online Journal]