mTORC1 activity is supported by spatial association with focal adhesions

Yoana Rabanal-Ruiz, Adam Byron, Alexander Wirth, Ralitsa Madsen, Lucia Sedlackova, Graeme Hewitt, Glyn Nelson, Julian Stingele, Jimi Wills, Tong Zhang, Andre Zeug, Reinhard Fässler, Bart Vanhaesebroeck, Oliver D K Maddocks, Evgeni Ponimaskin, Bernadette Carroll, Viktor I Korolchuk

Research output: Contribution to journalArticlepeer-review

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(Dibble and Cantley, 2015; Gonzalez and Hall, 2017; Rabanal-Ruiz and Korolchuk, 2018; Saxton and Sabatini, 2017). Here we show that translocation of lysosomes towards 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.
Original languageEnglish
JournalJournal of Cell Biology
Early online date26 Feb 2021
DOIs
Publication statusE-pub ahead of print - 26 Feb 2021

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