Eukaryotic initiation factor 6 regulates mechanical responses in endothelial cells
| Autor: | Adam N. Keen, Luke A. Payne, Vedanta Mehta, Alistair Rice, Lisa J. Simpson, Kar Lai Pang, Armando del Rio Hernandez, John S. Reader, Ellie Tzima |
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| Rok vydání: | 2022 |
| Předmět: |
Focal Adhesions
MAP Kinase Signaling System Endothelial Cells Cell Biology 06 Biological Sciences Mechanotransduction Cellular Article Biomechanical Phenomena Mice HEK293 Cells Peptide Initiation Factors Protein Biosynthesis Animals Humans Cattle Ribosomes 11 Medical and Health Sciences Cytoskeleton Developmental Biology |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Keen et al. discover a new role for eIF6, a protein classically known for its role in protein synthesis, in mechanotransduction, and the cellular response to force. These data provide a novel paradigm for how the cytoskeletal and translational machineries are linked. The repertoire of extratranslational functions of components of the protein synthesis apparatus is expanding to include control of key cell signaling networks. However, very little is known about noncanonical functions of members of the protein synthesis machinery in regulating cellular mechanics. We demonstrate that the eukaryotic initiation factor 6 (eIF6) modulates cellular mechanobiology. eIF6-depleted endothelial cells, under basal conditions, exhibit unchanged nascent protein synthesis, polysome profiles, and cytoskeleton protein expression, with minimal effects on ribosomal biogenesis. In contrast, using traction force and atomic force microscopy, we show that loss of eIF6 leads to reduced stiffness and force generation accompanied by cytoskeletal and focal adhesion defects. Mechanistically, we show that eIF6 is required for the correct spatial mechanoactivation of ERK1/2 via stabilization of an eIF6–RACK1–ERK1/2–FAK mechanocomplex, which is necessary for force-induced remodeling. These results reveal an extratranslational function for eIF6 and a novel paradigm for how mechanotransduction, the cellular cytoskeleton, and protein translation constituents are linked. |
| Databáze: | OpenAIRE |
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