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

Abstract

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.

Basally activated nonselective cation currents regulate the resting membrane potential in human and monkey colonic smooth muscle

“…Several TRP channels have been proposed to play important roles in the regulation of RMP in certain cell types (11,12). In the present study, analysis of human and monkey colonic SMC revealed TRPC1, C3, C4, C7, M2, M4, M6, M7, V1, and V2 transcript expression.…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…In neonatal human epidermal melanocytes, TRPM1 expression correlates with melanin content, suggesting that TRPM1 is critical to normal melanocyte pigmentation and thus represents a potential target for pigmentation disorders (Oancea et al, 2009;Hughes et al, 2012). TRPM1 regulates pigmentation by controlling melanin synthesis in skin melanocytes (Devi et al, 2009. TRPM2 ( Fig.…”

Trpm1

“…Reduced expression of TRPM1 in human melanocytes and mouse melanoma cell lines correlates with decreased melanin content, suggesting that TRPM1-mediated Ca 2+ homeostasis plays a role in the regulation of melanogenesis (Devi et al 2009;Oancea et al 2009). Interestingly, another group reported that human melanocytes express mGluR6, but not Goα, and that TRPM1 activity in human melanocytes is positively regulated by the mGluR6 signaling pathway (Devi et al 2013).…”