PT  - JOURNAL ARTICLE
AU  - Mirja T. Prentzell
AU  - Ulrike Rehbein
AU  - Marti Cadena Sandoval
AU  - Ann-Sofie De Meulemeester
AU  - Ralf Baumeister
AU  - Laura Brohée
AU  - Bianca Berdel
AU  - Mathias Bockwoldt
AU  - Bernadette Carroll
AU  - Andreas von Deimling
AU  - Constantinos Demetriades
AU  - Gianluca Figlia
AU  - Alexander M. Heberle
AU  - Ines Heiland
AU  - Birgit Holzwarth
AU  - Lukas A. Huber
AU  - Jacek Jaworski
AU  - Katharina Kern
AU  - Andrii Kopach
AU  - Viktor I. Korolchuk
AU  - Ineke van ’t Land-Kuper
AU  - Matylda Macias
AU  - Mark Nellist
AU  - Stefan Pusch
AU  - Michele Reil
AU  - Anja Reintjes
AU  - Friederike Reuter
AU  - Chloë Scheldeman
AU  - Eduard Stefan
AU  - Aurelio Teleman
AU  - Omar Torres-Quesada
AU  - Saskia Trump
AU  - Peter de Witte
AU  - Teodor Yordanov
AU  - Christiane A. Opitz
AU  - Kathrin Thedieck
TI  - G3BP1 tethers the TSC complex to lysosomes and suppresses mTORC1 in the absence of stress granules
AID  - 10.1101/2020.04.16.044081
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.16.044081
4099  - http://biorxiv.org/content/early/2020/04/22/2020.04.16.044081.short
4100  - http://biorxiv.org/content/early/2020/04/22/2020.04.16.044081.full
AB  - G3BP1 (Ras GTPase-activating protein-binding protein 1) is widely recognized as a core component of stress granules (SG), non-membranous RNA-protein-assemblies required for cellular survival under stress. We report that in the absence of SG, G3BP1 acts as lysosomal anchor of the Tuberous Sclerosis Complex (TSC) protein complex. By tethering the TSC complex to lysosomes, G3BP1 suppresses signaling through the metabolic master regulator mTORC1 (mechanistic target of rapamycin complex 1). Like the known TSC complex subunits, G3BP1 suppresses phenotypes related to mTORC1 hyperactivity in the context of tumors and neuronal dysfunction. Thus, G3BP1 is not only a core component of SG but also a key element of lysosomal TSC-mTORC1 signaling.Highlights The bona fide stress granule component G3BP1 is a key element of the TSC-mTORC1 signaling axis.tethers the TSC complex to lysosomes.prevents mTORC1 hyperactivation by metabolic stimuli.suppresses mTORC1-driven cancer cell motility and epileptiform activity.Competing Interest StatementThe authors have declared no competing interest.