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- W4220793555 abstract "ABSTRACT By acting both upstream and downstream of biochemical organizers of the cytoskeleton, physical forces function as central integrators of cell shape and movement. Here we use a combination of genetic, pharmacological, and optogenetic perturbations to probe the role of the conserved mechanoresponsive mTORC2 program in neutrophil polarity and motility. We find that the tension-based inhibition of leading edge signals (Rac, F-actin) that underlies protrusion competition is gated by the kinase-independent role of the complex, whereas the mTORC2 kinase arm is essential for regulation of Rho activity and Myosin II-based contraction at the trailing edge. Cells required mTORC2 for spatial and temporal coordination between the front and back polarity programs and persistent migration under confinement. mTORC2 is in a mechanosensory cascade, but membrane stretch did not suffice to stimulate mTORC2 unless the co-input PIP 3 was also present. Our work suggests that different signalling arms of mTORC2 regulate spatially and molecularly divergent cytoskeletal programs allowing efficient coordination of neutrophil shape and movement." @default.
- W4220793555 created "2022-04-03" @default.
- W4220793555 creator A5001678780 @default.
- W4220793555 creator A5039788638 @default.
- W4220793555 creator A5076309635 @default.
- W4220793555 date "2022-03-27" @default.
- W4220793555 modified "2023-09-27" @default.
- W4220793555 title "mTORC2 coordinates the leading and trailing edge cytoskeletal programs during neutrophil migration" @default.
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