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mTORC1 activity is supported by spatial association with focal adhesions

Lookup NU author(s): Dr Yoana Rabanal Ruiz, Lucy Sedlackova, Dr Glyn NelsonORCiD, Dr Bernadette Carroll, Dr Viktor Korolchuk



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.

Publication metadata

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


DOI: 10.1083/jcb.202004010

PubMed id: 33635313


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Funder referenceFunder name
Cancer Research UK Career Development Fellowship C53309/A19702
Wellcome Trust 218547/Z/19/Z