CALRETICULIN MODULATES CELL ADHESIVENESS VIA REGULATION OF VINCULIN EXPRESSION

Citation
M. Opas et al., CALRETICULIN MODULATES CELL ADHESIVENESS VIA REGULATION OF VINCULIN EXPRESSION, The Journal of cell biology, 135(6), 1996, pp. 1913-1923
Citations number
70
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell Biology
Journal title
ISSN journal
0021-9525
Volume
135
Issue
6
Year of publication
1996
Part
2
Pages
1913 - 1923
Database
ISI
SICI code
0021-9525(1996)135:6<1913:CMCAVR>2.0.ZU;2-2
Abstract
Calreticulin is an ubiquitous and highly conserved high capacity Ca2+- binding protein that plays a major role in Ca2+ storage within the lum en of the ER. Here, using L fibroblast cell lines expressing different levels of calreticulin, we show that calreticulin plays a role in the control of cell adhesiveness via regulation of expression of vinculin , a cytoskeletal protein essential for cell-substratum and cell-cell a ttachments. Both vinculin protein and mRNA levels are increased in cel ls overexpressing calreticulin and are downregulated in cells expressi ng reduced level of calreticulin. Abundance of actin, talin, alpha(5) and beta(1) integrins, pp125 focal adhesion kinase, and alpha-catenin is not affected by the differential calreticulin expression, Overexpre ssion of calreticulin increases both cell-substratum and cell-cell adh esiveness of L fibroblasts that, most surprisingly, establish vinculin -rich cell-cell junctions. Upregulation of calreticulin also affects a dhesion-dependent phenomena such as cell motility (which decreases) an d cell spreading (which increases). Downregulation of calreticulin bri ngs about inverse effects. Cell adhesiveness is Ca2+ regulated. The le vel of calreticulin expression, however, has no effect on either the r esting cytoplasmic Ca2+ concentration or the magnitude of FGF-induced Ca2+ transients. Calreticulin, however, participates in Ca2+ homeostas is as its level of expression affects cell viability at low concentrat ions of extracellular Ca2+. Consequently, we infer that it is not the Ca2+ storage function of calreticulin that affects cell adhesiveness. Neither endogenous calreticulin nor overexpressed green fluorescent pr otein-calreticulin construct can be detected outside of the ER. Since all of the adhesion-related effects of differential calreticulin expre ssion can be explained by its regulation of vinculin expression, we co nclude that it is the ER-resident calreticulin that affects cellular a dhesiveness.