%0 Journal Article
%T Depletion of calpain2 accelerates epithelial barrier establishment and reduces growth factor-induced cell scattering.
%A Rasl J
%A Caslavsky J
%A Grusanovic J
%A Chvalova V
%A Kosla J
%A Adamec J
%A Grousl T
%A Klimova Z
%A Vomastek T
%J Cell Signal
%V 121
%N 0
%D 2024 Sep 10
%M 38996955
%F 4.85
%R 10.1016/j.cellsig.2024.111295
%X 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.