Codependencies of mTORC1 signaling and endolysosomal actin structures-Reference-Cited by-同舟云学术

Codependencies of mTORC1 signaling and endolysosomal actin structures

Published:2023-09-15 Issue:37 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Priya Amulya¹^ORCID,Antoine-Bally Sandra¹,Macé Anne-Sophie²,Monteiro Pedro¹,Sabatet Valentin³^ORCID,Remy David¹,Dingli Florent³^ORCID,Loew Damarys³^ORCID,Demetriades Constantinos⁴⁵^ORCID,Gautreau Alexis M.⁶^ORCID,Chavrier Philippe¹^ORCID

Affiliation:

1. Institut Curie, CNRS UMR144, PSL Research University, Research Center, Actin and Membrane Dynamics Laboratory, 26 rue d’Ulm, Paris 75248 Cedex 05, France.

2. Institut Curie, PSL Research University, Cell and Tissue Imaging Facility (PICT-IBiSA), 26 rue d’Ulm, Paris 75248 Cedex 05, France.

3. Institut Curie, PSL Research University, CurieCoreTech Mass Spectrometry Proteomics, 26 rue d’Ulm, Paris 75248 Cedex 05, France.

4. Max Planck Institute for Biology of Ageing (MPI-AGE), Cologne, Germany.

5. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

6. Laboratoire de Biologie Structurale de la Cellule, CNRS, École Polytechnique, Institut Polytechnique de Paris, Palaiseau, France.

Abstract

The mechanistic target of rapamycin complex 1 (mTORC1) is part of the amino acid sensing machinery that becomes activated on the endolysosomal surface in response to nutrient cues. Branched actin generated by WASH and Arp2/3 complexes defines endolysosomal microdomains. Here, we find mTORC1 components in close proximity to endolysosomal actin microdomains. We investigated for interactors of the mTORC1 lysosomal tether, RAGC, by proteomics and identified multiple actin filament capping proteins and their modulators. Perturbation of RAGC function affected the size of endolysosomal actin, consistent with a regulation of actin filament capping by RAGC. Reciprocally, the pharmacological inhibition of actin polymerization or alteration of endolysosomal actin obtained upon silencing of WASH or Arp2/3 complexes impaired mTORC1 activity. Mechanistically, we show that actin is required for proper association of RAGC and mTOR with endolysosomes. This study reveals an unprecedented interplay between actin and mTORC1 signaling on the endolysosomal system.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.add9084

Reference61 articles.

1. mTOR at the nexus of nutrition, growth, ageing and disease

2. Rags to riches: Amino acid sensing by the Rag GTPases in health and disease

3. The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging

4. A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids

5. Ragulator-Rag Complex Targets mTORC1 to the Lysosomal Surface and Is Necessary for Its Activation by Amino Acids