Depletion of calpain2 accelerates epithelial barrier establishment and reduces growth factor-induced cell scattering

Authors

Jan Rasl, Laboratory of Cell Signalling Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
Josef Caslavsky, Laboratory of Cell Signalling Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
Josipa Grusanovic, Laboratory of Cell Signalling Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
Vera Chvalova, Laboratory of Cell Signalling Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
Jan Kosla, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
Jiri Adamec, LSU Health Sciences Center - New OrleansFollow
Tomas Grousl, Laboratory of Cell Signalling Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
Zuzana Klimova, Laboratory of Cell Signalling Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
Tomas Vomastek, Laboratory of Cell Signalling Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic

Document Type

Article

Publication Date

7-10-2024

Publication Title

Cellular Signalling

Abstract

Calpain2 is a conventional member of the non-lysosomal calpain protease family that has been shown to affect the dynamics of focal and cell-cell adhesions by proteolyzing the components of adhesion complexes. Here, we inactivated calpain2 using CRISPR/Cas9 in epithelial MDCK cells. We show that depletion of calpain2 has multiple effects on cell morphology and function. Calpain2-depleted cells develop epithelial shape, however, they cover a smaller area, and cell clusters are more compact. Inactivation of calpain2 enhanced restoration of transepithelial electrical resistance after calcium switch, decreased cell migration, and delayed cell scattering induced by HGF/SF. In addition, calpain2 depletion prevented morphological changes induced by ERK2 overexpression. Interestingly, proteolysis of several calpain2 targets, including E-cadherin, β-catenin, talin, FAK, and paxillin, was not discernibly affected by calpain2 depletion. Taken together, these data suggest that calpain2 regulates the stability of cell-cell and cell-substratum adhesions indirectly without affecting the proteolysis of these adhesion complexes.

PubMed ID

38996955

Volume

121

Recommended Citation

Rasl, Jan; Caslavsky, Josef; Grusanovic, Josipa; Chvalova, Vera; Kosla, Jan; Adamec, Jiri; Grousl, Tomas; Klimova, Zuzana; and Vomastek, Tomas, "Depletion of calpain2 accelerates epithelial barrier establishment and reduces growth factor-induced cell scattering" (2024). School of Medicine Faculty Publications. 2922.
https://digitalscholar.lsuhsc.edu/som_facpubs/2922
10.1016/j.cellsig.2024.111295