Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light.
Transient receptor potential melastatin (TRPM) is a subfamily of ion channels that are involved in sensing taste, ambient temperature, low pH, osmolarity, and chemical ligands. Melastatin 1/TRPM1, the founding member, was originally identified as melanoma metastasis suppressor based on its expression in normal pigment cells in the skin and the eye but not in aggressive, metastasis-competent melanomas. The role of TRPM1 and its regulation in normal melanocytes and in melanoma progression is not understood. Here, we studied the relationship of TRPM1 expression to growth and differentiation of human epidermal melanocytes. TRPM1 expression and intracellular Ca(2+) levels are significantly lower in rapidly proliferating melanocytes compared to the slow growing, differentiated melanocytes. We show that lentiviral short hairpin RNA (shRNA)-mediated knockdown of TRPM1 results in reduced intracellular Ca(2+) and decreased Ca(2+) uptake suggesting a role for TRPM1 in Ca(2+) homeostasis in melanocytes. TRPM1 knockdown also resulted in a decrease in tyrosinase activity and intracellular melanin pigment. Expression of the tumor suppressor p53 by transfection or induction of endogenous p53 by ultraviolet B radiation caused repression of TRPM1 expression accompanied by decrease in mobilization of intracellular Ca(2+) and uptake of extracellular Ca(2+). These data suggest a role for TRPM1-mediated Ca(2+) homeostasis, which is also regulated by ultraviolet B, in melanogenesis.
Devi
Sulochana
S
Dept. of Dermatology, University of Wisconsin, School of Medicine and Public Health, Madison, Wisconsin 53706, USA.
Kedlaya
Rajendra
R
Maddodi
Nityanand
N
Bhat
Kumar M R
KM
Weber
Craig S
CS
Valdivia
Hector
H
Setaluri
Vijayasaradhi
V
D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects; D020868:Gene Silencing; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000378:metabolism* / Q000528:radiation effects; D050053:TRPM Cation Channels / Q000378:metabolism*; D014466:Ultraviolet Rays
D008543:Melanins; D050053:TRPM Cation Channels; C492059:TRPM1 protein, human; D002118:Calcium