Caldesmon inhibits nonmuscle cell contractility and interferes with the formation of focal adhesions

Helfman, D. M., Levy, E. T., Berthier, C., Shtutman, M., Riveline, D., Grosheva, I., Lachish-Zalait, A., Elbaum, M., Bershadsky, A. D. (October 1999) Caldesmon inhibits nonmuscle cell contractility and interferes with the formation of focal adhesions. Molecular Biology of the Cell , 10 (10). pp. 3097-112. ISSN 1059-1524 (Print)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/10512853
DOI: 10.1091/mbc.10.10.3097

Abstract

Caldesmon is known to inhibit the ATPase activity of actomyosin in a Ca(2+)-calmodulin-regulated manner. Although a nonmuscle isoform of caldesmon is widely expressed, its functional role has not yet been elucidated. We studied the effects of nonmuscle caldesmon on cellular contractility, actin cytoskeletal organization, and the formation of focal adhesions in fibroblasts. Transient transfection of nonmuscle caldesmon prevents myosin II-dependent cell contractility and induces a decrease in the number and size of tyrosine-phosphorylated focal adhesions. Expression of caldesmon interferes with Rho A-V14-mediated formation of focal adhesions and stress fibers as well as with formation of focal adhesions induced by microtubule disruption. This inhibitory effect depends on the actin- and myosin-binding regions of caldesmon, because a truncated variant lacking both of these regions is inactive. The effects of caldesmon are blocked by the ionophore A23187, thapsigargin, and membrane depolarization, presumably because of the ability of Ca(2+)-calmodulin or Ca(2+)-S100 proteins to antagonize the inhibitory function of caldesmon on actomyosin contraction. These results indicate a role for nonmuscle caldesmon in the physiological regulation of actomyosin contractility and adhesion-dependent signaling and further demonstrate the involvement of contractility in focal adhesion formation.

Item Type: Paper
Uncontrolled Keywords: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology Actomyosin/metabolism Animals Botulinum Toxins/pharmacology Calcimycin/pharmacology Calcium-Binding Proteins/metabolism Calmodulin-Binding Proteins/genetics/ metabolism Cell Line, Transformed Cytoskeleton/metabolism Enzyme Inhibitors/pharmacology Gene Expression Green Fluorescent Proteins Humans Ionophores/pharmacology Luminescent Proteins Microscopy, Fluorescence Microtubules/metabolism Mutation Nocodazole/pharmacology Rats Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Thapsigargin/pharmacology Transfection
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > ATPase
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > green fluorescent protein
Investigative techniques and equipment > microscopy
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
CSHL Authors:
Communities: CSHL labs > Helfman lab
Depositing User: Kathleen Darby
Date: October 1999
Date Deposited: 23 Apr 2014 18:52
Last Modified: 23 Apr 2014 18:52
PMCID: PMC25564
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29845

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