MKK6 increases the melanocyte dendricity through the regulation of Rho family GTPases

Abstract

Melanocyte dendrites serve as the principal conduit for melanosome transfer. The dendrite formation requires actin polymerization mediated by Rho family GTPases including RhoA, Rac1 and Cdc42. The aim of this study is to investigate and explore the involvement of p38 MAPK in melanocyte dendrite formation. We transduced melanoma cells with adenovirus harboring the expression cassette for constitutive active form of MKK6, an upstream MAPKK for p38 MAPK. We investigated the effect of melanogenic inducers on melanocyte dendricity, using SK-mel-24 melanoma cells because that this cell line is refractory to several melanogenic inducers in terms of melanogenesis. TPA-induced the phosphorylation of p38 MAPK and the elongation of dendrite length, suggesting that MKK6 may be involved in this process. Overexpression of the constitutive active form of MKK6 resulted in significant elongation of dendrites in the melanoma cell line SK-mel-24. Moreover, overexpression of MKK6 ultimately led to the upregulation of Cdc42 and Rac1, suggesting that MKK6 acts as a crucial upstream signaling molecule for Rho family GTPases. When overexpressed in normal human epidermal melanocytes, MKK6 led also the increase of dendrite length. These results suggest that MKK6 is an authentic regulator for melanocytes dendricity, through the modulation of Rho family GTPases.