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- W3048782014 abstract "Abstract Non-muscle myosin 2A (NM2A) is a key cytoskeletal enzyme that along with actin assembles into actomyosin filaments inside cells. NM2A is fundamental in cellular processes requiring force generation such as cell adhesion, motility and cell division, and plays important functions in different stages of development and during the progression of viral and bacterial infections. We previously identified a novel tyrosine phosphorylation on residue 158 (pTyr 158 ) in the motor domain of NM2A. This phosphorylation is dependent on Src kinase and is promoted by Listeria monocytogenes infection of epithelial cells, however its role is unknown. Here we show that Listeriolysin O (LLO), the pore-forming toxin (PFT) secreted by L. monocytogenes , is sufficient to trigger NM2A pTyr 158 by activating Src, an upstream regulator of actomyosin remodeling. We further address the role of NM2A pTyr 158 on the organization and dynamics of the actomyosin cytoskeleton and find that, by controlling the activation of the NM2A, the status of the pTyr 158 alters cytoskeletal organization, dynamics of focal adhesions and cell motility. In vitro , we observe that non-phosphorylatable and phospho-mimetic versions of NM2A at Tyr 158 display motor and ATPase activities similar to the wild-type NM2A, which indicates that the phenotype of these mutants in cells is independent of their ability to translocate actin filaments. Importantly, we find the regulation of this phosphorylation site to be of physiological relevance in Caenorhabditis elegans , in particular in response to intoxication by a PFT and to heat shock. We conclude that the control of the phosphorylation status at NM2A Tyr 158 is a conserved trait that contributes to the regulation of actomyosin dynamics and the ability of cells to respond to bacterial infection. We propose Src-dependent NM2A pTyr 158 as a novel layer of regulation of the actomyosin cytoskeleton." @default.
- W3048782014 created "2020-08-18" @default.
- W3048782014 creator A5014984934 @default.
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- W3048782014 creator A5086287356 @default.
- W3048782014 creator A5086529456 @default.
- W3048782014 date "2020-08-13" @default.
- W3048782014 modified "2023-10-01" @default.
- W3048782014 title "Src-dependent NM2A tyrosine-phosphorylation regulates actomyosin dynamics" @default.
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