mTORC1 activity is supported by spatial association with focal adhesions.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
03 05 2021
03 05 2021
Historique:
received:
02
04
2020
revised:
21
11
2020
accepted:
29
01
2021
entrez:
26
2
2021
pubmed:
27
2
2021
medline:
29
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33635313
pii: 211831
doi: 10.1083/jcb.202004010
pmc: PMC7923692
pii:
doi:
Substances chimiques
Amino Acids
0
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Research UK
ID : C53309/A19702
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 218547/Z/19/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 25722
Pays : United Kingdom
Organisme : European Research Council
ID : 801750
Pays : International
Organisme : Wellcome Trust
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 Rabanal-Ruiz et al.
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