| Literature DB >> 33497611 |
Mirja Tamara Prentzell1, Ulrike Rehbein2, Marti Cadena Sandoval3, Ann-Sofie De Meulemeester4, Ralf Baumeister5, Laura Brohée6, Bianca Berdel7, Mathias Bockwoldt8, Bernadette Carroll9, Suvagata Roy Chowdhury10, Andreas von Deimling11, Constantinos Demetriades12, Gianluca Figlia13, Mariana Eca Guimaraes de Araujo14, Alexander M Heberle3, Ines Heiland8, Birgit Holzwarth15, Lukas A Huber16, Jacek Jaworski17, Magdalena Kedra17, Katharina Kern7, Andrii Kopach17, Viktor I Korolchuk18, Ineke van 't Land-Kuper19, Matylda Macias17, Mark Nellist20, Wilhelm Palm10, Stefan Pusch11, Jose Miguel Ramos Pittol21, Michèle Reil7, Anja Reintjes21, Friederike Reuter7, Julian R Sampson22, Chloë Scheldeman23, Aleksandra Siekierska4, Eduard Stefan21, Aurelio A Teleman13, Laura E Thomas24, Omar Torres-Quesada21, Saskia Trump25, Hannah D West22, Peter de Witte4, Sandra Woltering7, Teodor E Yordanov26, Justyna Zmorzynska17, Christiane A Opitz27, Kathrin Thedieck28.
Abstract
Ras 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.Entities:
Keywords: G3BP1; G3BP2; TSC complex; cancer; lysosome; mTORC1; metabolism; neuronal function; stress granule
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Year: 2021 PMID： 33497611 PMCID： PMC7868890 DOI： 10.1016/j.cell.2020.12.024
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582