The alpha isoform of protein kinase C is involved in signaling the response of desmosomes to wounding in cultured epithelial cells

Wallis, S., Lloyd, S., Wise, I., Ireland, G., Fleming, T.P. and Garrod, D. (2000) The alpha isoform of protein kinase C is involved in signaling the response of desmosomes to wounding in cultured epithelial cells. Molecular Biology of the Cell, 11 (3), 1077-1092.

Abstract

Initiation of reepithelialization upon wounding is still poorly understood. To enhance this understanding, we focus here on changes in the adhesive state of desmosomes of cultured Madin-Darby canine kidney cells in response to wounding of confluent cell sheets. Previous results show that desmosomal adhesion in Madin-Darby canine kidney cells changes from a calcium-dependent state to calcium independence in confluent cell sheets. We show that this change, which requires culture confluence to develop, is rapidly reversed upon wounding of confluent cell sheets. Moreover, the change to calcium dependence in wound edge cells is propagated to cells hundreds of micrometers away from the wound edge. Rapid transition from calcium independence to calcium dependence also occurs when cells are treated with phorbol esters that activate PKC. PKC inhibitors, including the conventional isoform inhibitor Gö6976, cause rapid transition from calcium dependence to calcium independence, even in subconfluent cells. The cellular location of the isoform of PKC correlates with the calcium dependence of desmosomes. Upon monolayer wounding, PKC translocates rapidly to the cell periphery, becomes Triton X-100 insoluble, and also becomes concentrated in lamellipodia. The PKC translocation upon wounding precedes both the increase in PKC activity in the membrane fraction and the reversion of desmosomes to calcium dependence. Specific depletion of PKC with an antisense oligonucleotide increases the number of cells with calcium-independent desmosomes. These results show that PKC participates in a novel signaling pathway that modulates desmosomal adhesion in response to wounding.

This record has no associated files available for download.

Contributors

Download statistics