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mTORC1 activity is supported by spatial association with focal adhesions

Rabanal-Ruiz, Y; Byron, A; Wirth, A; Madsen, R; Sedlackova, L; Hewitt, G; Nelson, G; ... Korolchuk, VI; + view all (2021) mTORC1 activity is supported by spatial association with focal adhesions. Journal of Cell Biology , 220 (5) , Article e202004010. 10.1083/jcb.202004010. Green open access

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Abstract

The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogenic and stress signals to control growth and metabolism. Activation of mTORC1 by amino acids and growth factors involves recruitment of the complex to the lysosomal membrane and is further supported by lysosome distribution to the cell periphery. Here, we show that translocation of lysosomes toward the cell periphery brings mTORC1 into proximity with focal adhesions (FAs). We demonstrate that FAs constitute discrete plasma membrane hubs mediating growth factor signaling and amino acid input into the cell. FAs, as well as the translocation of lysosome-bound mTORC1 to their vicinity, contribute to both peripheral and intracellular mTORC1 activity. Conversely, lysosomal distribution to the cell periphery is dispensable for the activation of mTORC1 constitutively targeted to FAs. This study advances our understanding of spatial mTORC1 regulation by demonstrating that the localization of mTORC1 to FAs is both necessary and sufficient for its activation by growth-promoting stimuli.

Type: Article
Title: mTORC1 activity is supported by spatial association with focal adhesions
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1083/jcb.202004010
Publisher version: http://dx.doi.org/10.1083/jcb.202004010
Language: English
Additional information: © 2021 Rabanal-Ruiz et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/ licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10123737
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