Calreticulin modulates cell adhesiveness via regulation of vinculin expression

Michal Opas, Malgorzata Szewczenko-Pawlikowski, Greta K. Jass, Nasrin Mesaeli, Marek Michalak

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Calreticulin is an ubiquitous and highly conserved high capacity Ca2+-binding protein that plays a major role in Ca2+ storage within the lumen 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 attachments. Both vinculin protein and mRNA levels are increased in cells overexpressing calreticulin and are downregulated in cells expressing reduced level of calreticulin. Abundance of actin, talin, α5 and β1 integrins, pp125 focal adhesion kinase, and α-catenin is not affected by the differential calreticulin expression. Overexpression of calreticulin increases both cell-substratum and cell-cell adhesiveness of L fibroblasts that, most surprisingly, establish vinculin-rich cell-cell junctions. Upregulation of calreticulin also affects adhesion-dependent phenomena such as cell motility (which decreases) and cell spreading (which increases). Downregulation of calreticulin brings about inverse effects. Cell adhesiveness is Ca2+ regulated. The level of calreticulin expression, however, has no effect on either the resting cytoplasmic Ca2+ concentration or the magnitude of FGF-induced Ca2+ transients. Calreticulin, however, participates in Ca2+ homeostasis as its level of expression affects cell viability at low concentrations 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 protein calreticulin construct can be detected outside of the ER. Since all of the adhesion-related effects of differential calreticulin expression can be explained by its regulation of vinculin expression, we conclude that it is the ER-resident calreticulin that affects cellular adhesiveness.

Original languageEnglish
Pages (from-to)1913-1923
Number of pages11
JournalJournal of Cell Biology
Volume135
Issue number6 II
DOIs
Publication statusPublished - 1996
Externally publishedYes

Fingerprint

Calreticulin
Vinculin
Adhesiveness
Down-Regulation
Fibroblasts
Talin
Catenins
Focal Adhesion Protein-Tyrosine Kinases
Cytoskeletal Proteins
Intercellular Junctions

ASJC Scopus subject areas

  • Cell Biology

Cite this

Calreticulin modulates cell adhesiveness via regulation of vinculin expression. / Opas, Michal; Szewczenko-Pawlikowski, Malgorzata; Jass, Greta K.; Mesaeli, Nasrin; Michalak, Marek.

In: Journal of Cell Biology, Vol. 135, No. 6 II, 1996, p. 1913-1923.

Research output: Contribution to journalArticle

Opas, M, Szewczenko-Pawlikowski, M, Jass, GK, Mesaeli, N & Michalak, M 1996, 'Calreticulin modulates cell adhesiveness via regulation of vinculin expression', Journal of Cell Biology, vol. 135, no. 6 II, pp. 1913-1923. https://doi.org/10.1083/jcb.135.6.1913
Opas, Michal ; Szewczenko-Pawlikowski, Malgorzata ; Jass, Greta K. ; Mesaeli, Nasrin ; Michalak, Marek. / Calreticulin modulates cell adhesiveness via regulation of vinculin expression. In: Journal of Cell Biology. 1996 ; Vol. 135, No. 6 II. pp. 1913-1923.
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