UV light activates a Gαq/11-coupled phototransduction pathway in human melanocytes.
While short exposure to solar ultraviolet radiation (UVR) can elicit increased skin pigmentation, a protective response mediated by epidermal melanocytes, chronic exposure can lead to skin cancer and photoaging. However, the molecular mechanisms that allow human skin to detect and respond to UVR remain incompletely understood. UVR stimulates a retinal-dependent signaling cascade in human melanocytes that requires GTP hydrolysis and phospholipase C β (PLCβ) activity. This pathway involves the activation of transient receptor potential A1 (TRPA1) ion channels, an increase in intracellular Ca(2+), and an increase in cellular melanin content. Here, we investigated the identity of the G protein and downstream elements of the signaling cascade and found that UVR phototransduction is Gαq/11 dependent. Activation of Gαq/11/PLCβ signaling leads to hydrolysis of phosphatidylinositol (4,5)-bisphosphate (PIP2) to generate diacylglycerol (DAG) and inositol 1, 4, 5-trisphosphate (IP3). We found that PIP2 regulated TRPA1-mediated photocurrents, and IP3 stimulated intracellular Ca(2+) release. The UVR-elicited Ca(2+) response appears to involve both IP3-mediated release from intracellular stores and Ca(2+) influx through TRPA1 channels, showing the fast rising phase of the former and the slow decay of the latter. We propose that melanocytes use a UVR phototransduction mechanism that involves the activation of a Gαq/11-dependent phosphoinositide cascade, and resembles light phototransduction cascades of the eye.
Department of Molecular Pharmacology, Physiology, and Biotechnology, and 2 Department of Neuroscience, Brown University, Providence, RI 02192.
Nicholas W
NW
Bellono
Julia A
JA
Najera
Elena
E
Oancea
D002478:Cells, Cultured; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism* / Q000528:radiation effects*; D057809:HEK293 Cells; D006801:Humans; D007231:Infant, Newborn; D055537:Light Signal Transduction / Q000502:physiology* / Q000528:radiation effects*; D008297:Male; D008544:Melanocytes / Q000378:metabolism* / Q000528:radiation effects*; D015398:Signal Transduction / Q000502:physiology; D014466:Ultraviolet Rays
D043802:GTP-Binding Protein alpha Subunits, Gq-G11