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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light

Departments of ¹Dermatology and ²Physiology, University of Wisconsin, School of Medicine and Public Health, Madison, Wisconsin

Submitted 2 March 2009 ; accepted in final form 30 June 2009

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 Ca²⁺ 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 Ca²⁺ and decreased Ca²⁺ uptake suggesting a role for TRPM1 in Ca²⁺ 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 Ca²⁺ and uptake of extracellular Ca²⁺. These data suggest a role for TRPM1-mediated Ca²⁺ homeostasis, which is also regulated by ultraviolet B, in melanogenesis.

melanocytes; melanoma; melanogenesis; differentiation

This article has been cited by other articles:

				S. Patel and R. Docampo In with the TRP Channels: Intracellular Functions for TRPM1 and TRPM2 Sci. Signal., November 3, 2009; 2(95): pe69 - pe69. [Abstract] [Full Text] [PDF]