G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling

Prentzell, Mirja Tamara; Rehbein, Ulrike; Sandoval, Marti Cadena; Meulemeester, Ann-Sofie De; Baumeister, Ralf; Brohée, Laura; Berdel, Bianca; Bockwoldt, Mathias; Carroll, Bernadette; Chowdhury, Suvagata Roy; Deimling, Andreas von; Demetriades, Constantinos; Figlia, Gianluca; Guimaraes, Mariana Eca; Heberle, Alexander M.; Heiland, Ines; Holzwarth, Birgit; Huber, Lukas A.; Jaworski, Jacek; Kedra, Magdalena; Kern, Katharina; Kopach, Andrii; Korolchuk, Viktor I.; 't, Ineke van; Macias, Matylda; Nellist, Mark; Palm, Wilhelm; Pusch, Stefan; Ramos, Jose Miguel; Reil, Michèle; Reintjes, Anja; Reuter, Friederike; Sampson, Julian R.; Scheldeman, Chloë; Siekierska, Aleksandra; Stefan, Eduard; Teleman, Aurelio A.; Thomas, Laura; Torres-Quesada, Omar; Trump, Saskia; West, Hannah D.; Witte, Peter de; Woltering, Sandra; Yordanov, Teodor E.; Zmorzynska, Justyna; Opitz, Christiane A.; Thedieck, Kathrin

doi:10.1016/j.cell.2020.12.024

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G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling

Mirja Tamara Prentzell, Ulrike Rehbein, Marti Cadena Sandoval, Ann-Sofie De Meulemeester, Ralf Baumeister, Laura Brohée, Bianca Berdel, Mathias Bockwoldt, Bernadette Carroll, Suvagata Roy Chowdhury, Andreas von Deimling, Constantinos Demetriades, Gianluca Figlia, Mariana Eca Guimaraes de Araujo, Alexander M. Heberle, Ines Heiland, Birgit Holzwarth, Lukas A. Huber, Jacek Jaworski, Magdalena Kedra, Katharina Kern, Andrii Kopach, Viktor I. Korolchuk, Ineke van 't Land-Kuper, Matylda Macias, Mark Nellist, Wilhelm Palm, Stefan Pusch, Jose Miguel Ramos Pittol, Michèle Reil, Anja Reintjes, Friederike Reuter, Julian R. Sampson, Chloë Scheldeman, Aleksandra Siekierska, Eduard Stefan, Aurelio A. Teleman, Laura Thomas

, Omar Torres-Quesada, Saskia Trump, Hannah D. West, Peter de Witte, Sandra Woltering, Teodor E. Yordanov, Justyna Zmorzynska, Christiane A. Opitz, Kathrin Thedieck

Cell, Volume: 184, Issue: 3, Pages: 655 - 674.e27

Swansea University Author: Laura Thomas

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DOI (Published version): 10.1016/j.cell.2020.12.024

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 (...

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Published in:	Cell
ISSN:	0092-8674
Published:	Elsevier BV 2021
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URI:	https://cronfa.swan.ac.uk/Record/cronfa58991
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first_indexed	2021-12-10T08:48:43Z
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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. 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spelling	2022-10-25T16:35:41.7672522 v2 58991 2021-12-10 G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling 6f80a1638d852bd88d37afe3aeb2fb62 0000-0002-8621-5285 Laura Thomas Laura Thomas true false 2021-12-10 BMS 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. Journal Article Cell 184 3 655 674.e27 Elsevier BV 0092-8674 TSC complex; mTORC1; G3BP1; G3BP2; lysosome; stress granule; metabolism; cancer; neuronal function 4 2 2021 2021-02-04 10.1016/j.cell.2020.12.024 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Another institution paid the OA fee 2022-10-25T16:35:41.7672522 2021-12-10T08:47:17.8475463 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Mirja Tamara Prentzell 1 Ulrike Rehbein 2 Marti Cadena Sandoval 3 Ann-Sofie De Meulemeester 4 Ralf Baumeister 5 Laura Brohée 6 Bianca Berdel 7 Mathias Bockwoldt 8 Bernadette Carroll 9 Suvagata Roy Chowdhury 10 Andreas von Deimling 11 Constantinos Demetriades 12 Gianluca Figlia 13 Mariana Eca Guimaraes de Araujo 14 Alexander M. Heberle 15 Ines Heiland 16 Birgit Holzwarth 17 Lukas A. Huber 18 Jacek Jaworski 19 Magdalena Kedra 20 Katharina Kern 21 Andrii Kopach 22 Viktor I. Korolchuk 23 Ineke van 't Land-Kuper 24 Matylda Macias 25 Mark Nellist 26 Wilhelm Palm 27 Stefan Pusch 28 Jose Miguel Ramos Pittol 29 Michèle Reil 30 Anja Reintjes 31 Friederike Reuter 32 Julian R. Sampson 33 Chloë Scheldeman 34 Aleksandra Siekierska 35 Eduard Stefan 36 Aurelio A. Teleman 37 Laura Thomas 0000-0002-8621-5285 38 Omar Torres-Quesada 39 Saskia Trump 40 Hannah D. West 41 Peter de Witte 42 Sandra Woltering 43 Teodor E. Yordanov 44 Justyna Zmorzynska 45 Christiane A. Opitz 46 Kathrin Thedieck 47 58991__21948__a47f6b11c00b47b58463b69efc6e4ff5.pdf 58991.pdf 2021-12-29T14:30:44.2367388 Output 14096670 application/pdf Version of Record true 2021 The Authors. This is an open access article under the CC BY-NC-ND license true eng http://creativecommons.org/licenses/by-nc-nd/4.0/
title	G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling
spellingShingle	G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling Laura Thomas
title_short	G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling
title_full	G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling
title_fullStr	G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling
title_full_unstemmed	G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling
title_sort	G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling
author_id_str_mv	6f80a1638d852bd88d37afe3aeb2fb62
author_id_fullname_str_mv	6f80a1638d852bd88d37afe3aeb2fb62_***_Laura Thomas
author	Laura Thomas
author2	Mirja Tamara Prentzell Ulrike Rehbein Marti Cadena Sandoval Ann-Sofie De Meulemeester Ralf Baumeister Laura Brohée Bianca Berdel Mathias Bockwoldt Bernadette Carroll Suvagata Roy Chowdhury Andreas von Deimling Constantinos Demetriades Gianluca Figlia Mariana Eca Guimaraes de Araujo Alexander M. Heberle Ines Heiland Birgit Holzwarth Lukas A. Huber Jacek Jaworski Magdalena Kedra Katharina Kern Andrii Kopach Viktor I. Korolchuk Ineke van 't Land-Kuper Matylda Macias Mark Nellist Wilhelm Palm Stefan Pusch Jose Miguel Ramos Pittol Michèle Reil Anja Reintjes Friederike Reuter Julian R. Sampson Chloë Scheldeman Aleksandra Siekierska Eduard Stefan Aurelio A. Teleman Laura Thomas Omar Torres-Quesada Saskia Trump Hannah D. West Peter de Witte Sandra Woltering Teodor E. Yordanov Justyna Zmorzynska Christiane A. Opitz Kathrin Thedieck
format	Journal article
container_title	Cell
container_volume	184
container_issue	3
container_start_page	655
publishDate	2021
institution	Swansea University
issn	0092-8674
doi_str_mv	10.1016/j.cell.2020.12.024
publisher	Elsevier BV
college_str	Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id	facultyofmedicinehealthandlifesciences
hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id	facultyofmedicinehealthandlifesciences
hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description	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.
published_date	2021-02-04T04:15:57Z
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score	11.013148

G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling

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