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

Citation
S. Wallis et al., The alpha isoform of protein kinase C is involved in signaling the response of desmosomes to wounding in cultured epithelial cells, MOL BIOL CE, 11(3), 2000, pp. 1077-1092
Citations number
74
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR BIOLOGY OF THE CELL
ISSN journal
10591524 → ACNP
Volume
11
Issue
3
Year of publication
2000
Pages
1077 - 1092
Database
ISI
SICI code
1059-1524(200003)11:3<1077:TAIOPK>2.0.ZU;2-F
Abstract
Initiation of reepithelialization upon wounding is still poorly understood. To enhance this understanding, we focus here on changes in the adhesive st ate of desmosomes of cultured Madin-Darby canine kidney cells in response t o wounding of confluent cell sheets. Previous results show that desmosomal adhesion in Madin-Darby canine kidney cells changes from a calcium-dependen t 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 dep endence in wound edge cells is propagated to cells hundreds of micrometers away from the wound edge. Rapid transition from calcium independence to cal cium dependence also occurs when cells are treated with phorbol esters that activate PKC. PKC inhibitors, including the conventional isoform inhibitor Go6976, cause rapid transition from calcium dependence to calcium independ ence, even in subconfluent cells. The cellular location of the a isoform of PKC correlates with the calcium dependence of desmosomes. Upon monolayer w ounding, PKC alpha translocates rapidly to the cell periphery, becomes Trit on X-100 insoluble, and also becomes concentrated in lamellipodia. The PKC alpha a translocation upon wounding precedes both the increase in PKC activ ity in the membrane fraction and the reversion of desmosomes to calcium dep endence. Specific depletion of PKC alpha with an antisense oligonucleotide increases the number of cells with calcium-independent desmosomes. These re sults show that PKC alpha participates in a novel signaling pathway that mo dulates desmosomal adhesion in response to wounding.