Beta-catenin regulates melanocyte dendricity through the modulation of PKCzeta and PKCdelta.
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.
Kim
Jin-Hwa
JH
Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Korea.
Sohn
Kyung-Cheol
KC
Choi
Tae-Young
TY
Kim
Mi Yoon
MY
Ando
Hideya
H
Choi
Sun Ja
SJ
Kim
Sooil
S
Lee
Young Ho
YH
Lee
Jeung-Hoon
JH
Kim
Chang Deok
CD
Yoon
Tae-Jin
TJ
D003599:Cytoskeleton / Q000378:metabolism; D003712:Dendrites / Q000201:enzymology*; D000078404:Epidermal Cells; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000201:enzymology*; D008954:Models, Biological; D010858:Pigmentation; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*; D000099221:Protein Kinase C zeta
D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D051176:beta Catenin; D000099221:Protein Kinase C zeta