beta-Catenin regulates melanocyte dendricity through the modulation of PKC zeta and PKC delta

Abstract

P>The Wnt/beta-catenin signaling pathway is involved in the melanocyte differentiation and melanoma development. However, the effect of beta-catenin for dendrite formation has not been clearly elucidated yet in normal human epidermal melanocytes (NHEM). To investigate the effect of beta-catenin, we transduced NHEM with recombinant adenovirus expressing beta-catenin. Forced expression of beta-catenin led to the dramatic morphological changes of NHEM, including the reduction of dendrite length and enlargement of cell body. Concomitantly with, the protein levels for dendrite formation-related molecules, such as Rac1 and Cdc42, were markedly decreased. In addition, phosphorylation of p38 MAPK was significantly reduced by beta-catenin, potentiating its inhibitory role for dendrite formation. Interestingly, overexpression of beta-catenin led to the increase of protein kinase C zeta (PKC zeta) level, while protein kinase C delta (PKC delta) was decreased by beta-catenin, suggesting that those PKCs were beta-catenin-downstream modulators in NHMC. When PKC zeta was overexpressed, dendrites were shortened, with the reduced protein levels for Rac1 and Cdc42. In contrast, PKC delta overexpression led to the elongation of dendrites, with the increased levels for Rac1 and Cdc42. These results suggest that beta-catenin play an inhibitory role for dendrite formation through the modulation of PKC zeta and PKC delta.