TSC2 regulates lysosome biogenesis via a non-canonical RAGC and TFEB-dependent mechanism

Nicola Alesi; Elie W. Akl; Damir Khabibullin; Heng-Jia Liu; Anna S. Nidhiry; Emma R. Garner; Harilaos Filippakis; Hilaire C. Lam; Wei Shi; Srinivas R. Viswanathan; Manrico Morroni; Shawn M. Ferguson; Elizabeth P. Henske

doi:10.1038/s41467-021-24499-6

Nature Communications (Jul 2021)

TSC2 regulates lysosome biogenesis via a non-canonical RAGC and TFEB-dependent mechanism

Nicola Alesi,
Elie W. Akl,
Damir Khabibullin,
Heng-Jia Liu,
Anna S. Nidhiry,
Emma R. Garner,
Harilaos Filippakis,
Hilaire C. Lam,
Wei Shi,
Srinivas R. Viswanathan,
Manrico Morroni,
Shawn M. Ferguson,
Elizabeth P. Henske

Affiliations

Nicola Alesi: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Elie W. Akl: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Damir Khabibullin: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Heng-Jia Liu: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Anna S. Nidhiry: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Emma R. Garner: Department of Medical Oncology, Dana–Farber Cancer Institute, Harvard Medical School
Harilaos Filippakis: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Hilaire C. Lam: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Wei Shi: Department of Surgery, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California
Srinivas R. Viswanathan: Department of Medical Oncology, Dana–Farber Cancer Institute, Harvard Medical School
Manrico Morroni: Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, School of Medicine, Università Politecnica delle Marche
Shawn M. Ferguson: Department of Cell Biology, Yale University School of Medicine
Elizabeth P. Henske: Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School

DOI: https://doi.org/10.1038/s41467-021-24499-6
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 12

Abstract

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Tuberous sclerosis complex (TSC) is a multiorgan disease that can lead to hyperactive mTORC1 due to deficient TSC1 or TSC2 protein function. Here, the authors find that despite high mTORC1 activity, TFEB localizes to the nucleus and drives lysosomal gene expression via a non-canonical Rag-dependent mechanism.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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