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Lookup NU author(s): Marti Cadena Sandoval,
Dr Bernadette Carroll,
Dr Viktor Korolchuk
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2021 The AuthorsDistinct from their contributions to stress granules, G3BPs regulate mTORC1 activity through spatial control of the TSC complex.© 2021 The AuthorsRas GTPase-activating protein-binding proteins 1 and 2 (G3BP1 and G3BP2, respectively) are widely recognized as core components of stress granules (SGs). We report that G3BPs reside at the cytoplasmic surface of lysosomes. They act in a non-redundant manner to anchor the tuberous sclerosis complex (TSC) protein complex to lysosomes and suppress activation of the metabolic master regulator mechanistic target of rapamycin complex 1 (mTORC1) by amino acids and insulin. Like the TSC complex, G3BP1 deficiency elicits phenotypes related to mTORC1 hyperactivity. In the context of tumors, low G3BP1 levels enhance mTORC1-driven breast cancer cell motility and correlate with adverse outcomes in patients. Furthermore, G3bp1 inhibition in zebrafish disturbs neuronal development and function, leading to white matter heterotopia and neuronal hyperactivity. Thus, G3BPs are not only core components of SGs but also a key element of lysosomal TSC-mTORC1 signaling.
Author(s): Prentzell MT, Rehbein U, Cadena Sandoval M, De Meulemeester A-S, Baumeister R, Brohee L, Berdel B, Bockwoldt M, Carroll B, Chowdhury SR, von Deimling A, Demetriades C, Figlia G, de Araujo MEG, Heberle AM, Heiland I, Holzwarth B, Huber LA, Jaworski J, Kedra M, Kern K, Kopach A, Korolchuk VI, van 't Land-Kuper I, Macias M, Nellist M, Palm W, Pusch S, Ramos Pittol JM, Reil M, Reintjes A, Reuter F, Sampson JR, Scheldeman C, Siekierska A, Stefan E, Teleman AA, Thomas LE, Torres-Quesada O, Trump S, West HD, de Witte P, Woltering S, Yordanov TE, Zmorzynska J, Opitz CA, Thedieck K
Publication type: Article
Publication status: Published
Print publication date: 04/02/2021
Online publication date: 25/01/2021
Acceptance date: 14/12/2020
Date deposited: 01/04/2021
ISSN (print): 0092-8674
ISSN (electronic): 1097-4172
Publisher: Elsevier B.V.
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