Mechanosensing through direct binding of tensed F-actin by LIM domains
| Autor: | Clare M. Waterman, Rui Gong, Lucas Axiotakis, Santiago Reyes, Xiaoyu Sun, Mark A. Smith, Donovan Y.Z. Phua, Robert C. Cail, Mary C. Beckerle, Elizabeth Blankman, Gregory M. Alushin |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Phenylalanine
macromolecular substances Mechanotransduction Cellular General Biochemistry Genetics and Molecular Biology Article Zyxin Mice 03 medical and health sciences 0302 clinical medicine Animals Humans Cytoskeleton Molecular Biology Conserved Sequence Actin Paxillin 030304 developmental biology LIM domain Cell Nucleus Focal Adhesions 0303 health sciences biology Chemistry Cell Biology LIM Domain Proteins Actin cytoskeleton Actins Biomechanical Phenomena FHL2 Cell biology Actin Cytoskeleton Cytoplasm 030220 oncology & carcinogenesis biology.protein 030217 neurology & neurosurgery Developmental Biology Protein Binding |
| Zdroj: | Dev Cell |
| DOI: | 10.1101/2020.03.06.979245 |
| Popis: | SummaryMechanical signals transmitted through the cytoplasmic actin cytoskeleton must be relayed to the nucleus to control gene expression. LIM domains are protein-protein interaction modules found in cytoskeletal proteins and transcriptional regulators; however, it is unclear if there is a direct link between these two functions. Here we identify three LIM protein families (zyxin, paxillin, and FHL) whose members preferentially localize to the actin cytoskeleton in mechanically-stimulated cells through their tandem LIM domains. A minimal actin-myosin reconstitution system reveals that representatives of all three families directly bind F-actin only in the presence of mechanical force. Point mutations at a site conserved in each LIM domain of these proteins selectively disrupt tensed F-actin bindingin vitroand cytoskeletal localization in cells, demonstrating a common, avidity-based mechanism. Finally, we find that binding to tensed F-actin in the cytoplasm excludes the cancer-associated transcriptional co-activator FHL2 from the nucleus in stiff microenvironments. This establishes direct force-activated F-actin binding by FHL2 as a mechanosensing mechanism. Our studies suggest that force-dependent sequestration of LIM proteins on the actin cytoskeleton could be a general mechanism for controlling nuclear localization to effect mechanical signaling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|