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Lookup NU author(s): Dr Yoana Rabanal Ruiz, Lucy Sedlackova, Dr Glyn NelsonORCiD, Dr Bernadette Carroll, Professor Viktor KorolchukORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021 Rabanal-Ruiz et al.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.
Author(s): Rabanal-Ruiz Y, Byron A, Wirth A, Madsen R, Sedlackova L, Hewitt G, Nelson G, Stingele J, Wills JC, Zhang T, Zeug A, Fassler R, Vanhaesebroeck B, Maddocks ODK, Ponimaskin E, Carroll B, Korolchuk VI
Publication type: Article
Publication status: Published
Journal: Journal of Cell Biology
Year: 2021
Volume: 220
Issue: 5
Print publication date: 03/05/2021
Online publication date: 26/02/2021
Acceptance date: 29/01/2021
Date deposited: 09/04/2021
ISSN (print): 0021-9525
ISSN (electronic): 1540-8140
Publisher: Rockefeller University Press
URL: https://doi.org/10.1083/jcb.202004010
DOI: 10.1083/jcb.202004010
PubMed id: 33635313
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