Prentzell, Mirja Tamara, Rehbein, Ulrike ORCID: 0000-0002-9104-4222, Sandoval, Marti Cadena, De Meulemeester, Ann-Sofie ORCID: 0000-0001-8490-5816, Baumeister, Ralf, Brohee, Laura, Berdel, Bianca, Bockwoldt, Mathias, Carroll, Bernadette ORCID: 0000-0001-5673-9371, Chowdhury, Suvagata Roy, von Deimling, Andreas ORCID: 0000-0002-5863-540X, Demetriades, Constantinos ORCID: 0000-0001-7813-7726, Figlia, Gianluca, de Araujo, Mariana Eca Guimaraes, Heberle, Alexander M., Heiland, Ines, Holzwarth, Birgit, Huber, Lukas A., Jaworski, Jacek ORCID: 0000-0001-8760-7865, Kedra, Magdalena, Kern, Katharina, Kopach, Andrii ORCID: 0000-0002-0614-9717, Korolchuk, Viktor, I, van't Land-Kuper, Ineke, Macias, Matylda ORCID: 0000-0002-0412-7151, Nellist, Mark, Palm, Wilhelm, Pusch, Stefan, Pittol, Jose Miguel Ramos, Reil, Michele, Reintjes, Anja, Reuter, Friederike, Sampson, Julian R., Scheldeman, Chloe, Siekierska, Aleksandra ORCID: 0000-0003-4907-605X, Stefan, Eduard, Teleman, Aurelio A., Thomas, Laura E., Torres-Quesada, Omar, Trump, Saskia ORCID: 0000-0002-9894-1807, West, Hannah D., de Witte, Peter ORCID: 0000-0002-9989-9567, Woltering, Sandra, Yordanov, Teodor E., Zmorzynska, Justyna ORCID: 0000-0001-8489-8732, Opitz, Christiane A. and Thedieck, Kathrin ORCID: 0000-0002-9069-2930 (2021). G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling. Cell, 184 (3). S. 655 - 702. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Prentzell, Mirja TamaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rehbein, UlrikeUNSPECIFIEDorcid.org/0000-0002-9104-4222UNSPECIFIED
Sandoval, Marti CadenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Meulemeester, Ann-SofieUNSPECIFIEDorcid.org/0000-0001-8490-5816UNSPECIFIED
Baumeister, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brohee, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berdel, BiancaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bockwoldt, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carroll, BernadetteUNSPECIFIEDorcid.org/0000-0001-5673-9371UNSPECIFIED
Chowdhury, Suvagata RoyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Deimling, AndreasUNSPECIFIEDorcid.org/0000-0002-5863-540XUNSPECIFIED
Demetriades, ConstantinosUNSPECIFIEDorcid.org/0000-0001-7813-7726UNSPECIFIED
Figlia, GianlucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Araujo, Mariana Eca GuimaraesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heberle, Alexander M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heiland, InesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holzwarth, BirgitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huber, Lukas A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jaworski, JacekUNSPECIFIEDorcid.org/0000-0001-8760-7865UNSPECIFIED
Kedra, MagdalenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kern, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kopach, AndriiUNSPECIFIEDorcid.org/0000-0002-0614-9717UNSPECIFIED
Korolchuk, Viktor, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van't Land-Kuper, InekeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Macias, MatyldaUNSPECIFIEDorcid.org/0000-0002-0412-7151UNSPECIFIED
Nellist, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palm, WilhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pusch, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pittol, Jose Miguel RamosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reil, MicheleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reintjes, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reuter, FriederikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sampson, Julian R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheldeman, ChloeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siekierska, AleksandraUNSPECIFIEDorcid.org/0000-0003-4907-605XUNSPECIFIED
Stefan, EduardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teleman, Aurelio A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, Laura E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Torres-Quesada, OmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trump, SaskiaUNSPECIFIEDorcid.org/0000-0002-9894-1807UNSPECIFIED
West, Hannah D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Witte, PeterUNSPECIFIEDorcid.org/0000-0002-9989-9567UNSPECIFIED
Woltering, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yordanov, Teodor E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zmorzynska, JustynaUNSPECIFIEDorcid.org/0000-0001-8489-8732UNSPECIFIED
Opitz, Christiane A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thedieck, KathrinUNSPECIFIEDorcid.org/0000-0002-9069-2930UNSPECIFIED
URN: urn:nbn:de:hbz:38-606334
DOI: 10.1016/j.cell.2020.12.024
Journal or Publication Title: Cell
Volume: 184
Number: 3
Page Range: S. 655 - 702
Date: 2021
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4172
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GTPASE-ACTIVATING PROTEIN; STRESS GRANULE FORMATION; TUBEROUS SCLEROSIS; MESSENGER-RNA; TSC1-TSC2 COMPLEX; MAMMALIAN TARGET; CELL-GROWTH; INTELLECTUAL DISABILITY; S6 KINASE; RAPAMYCINMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60633

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