Beta-catenin regulates melanocyte dendricity through the modulation of PKCzeta and PKCdelta

Pigment Cell Melanoma Res. 2010 Jun;23(3):385-93. doi: 10.1111/j.1755-148X.2010.00695.x. Epub 2010 Mar 13.

Abstract

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 (PKCzeta) level, while protein kinase C delta (PKCdelta) was decreased by beta-catenin, suggesting that those PKCs were beta-catenin-downstream modulators in NHMC. When PKCzeta was overexpressed, dendrites were shortened, with the reduced protein levels for Rac1 and Cdc42. In contrast, PKCdelta 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 PKCzeta and PKCdelta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytoskeleton / metabolism
  • Dendrites / enzymology*
  • Epidermal Cells
  • Humans
  • Male
  • Melanocytes / enzymology*
  • Models, Biological
  • Pigmentation
  • Protein Kinase C / metabolism*
  • Protein Kinase C-delta / metabolism*
  • Signal Transduction
  • beta Catenin / metabolism*

Substances

  • beta Catenin
  • protein kinase C zeta
  • Protein Kinase C
  • Protein Kinase C-delta