An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss

Kaushal Asrani; Juhyung Woo; Adrianna A. Mendes; Ethan Schaffer; Thiago Vidotto; Clarence Rachel Villanueva; Kewen Feng; Lia Oliveira; Sanjana Murali; Hans B. Liu; Daniela C. Salles; Brandon Lam; Pedram Argani; Tamara L. Lotan

doi:10.1038/s41467-022-34617-7

Nature Communications (Nov 2022)

An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss

Kaushal Asrani,
Juhyung Woo,
Adrianna A. Mendes,
Ethan Schaffer,
Thiago Vidotto,
Clarence Rachel Villanueva,
Kewen Feng,
Lia Oliveira,
Sanjana Murali,
Hans B. Liu,
Daniela C. Salles,
Brandon Lam,
Pedram Argani,
Tamara L. Lotan

Affiliations

Kaushal Asrani: Department of Pathology, Johns Hopkins University School of Medicine
Juhyung Woo: Department of Pathology, Johns Hopkins University School of Medicine
Adrianna A. Mendes: Department of Pathology, Johns Hopkins University School of Medicine
Ethan Schaffer: Department of Pathology, Johns Hopkins University School of Medicine
Thiago Vidotto: Department of Pathology, Johns Hopkins University School of Medicine
Clarence Rachel Villanueva: Department of Pathology, Johns Hopkins University School of Medicine
Kewen Feng: Department of Oncology, Johns Hopkins University School of Medicine
Lia Oliveira: Department of Pathology, Johns Hopkins University School of Medicine
Sanjana Murali: Department of Pathology, Johns Hopkins University School of Medicine
Hans B. Liu: Department of Pathology, Johns Hopkins University School of Medicine
Daniela C. Salles: Department of Pathology, Johns Hopkins University School of Medicine
Brandon Lam: Department of Pathology, Johns Hopkins University School of Medicine
Pedram Argani: Department of Pathology, Johns Hopkins University School of Medicine
Tamara L. Lotan: Department of Pathology, Johns Hopkins University School of Medicine

DOI: https://doi.org/10.1038/s41467-022-34617-7
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 15

Abstract

Read online

The MiT/TFE transcription factors are phosphorylated and inactivated by mTORC1. Here, authors demonstrate that TFEB is paradoxically hypophosphorylated and activated in cells with TSC2 loss due to impaired lysosomal recruitment of the FLCN:FNIP2 complex in renal cells.

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/

About the journal