TORC1 Determines Fab1 Lipid Kinase

De Virgilio, Claudio; Chen, Zilei; Carpio Malia, Pedro; Hatakeyama, Riko; Nicastro, Raffaele; Hu, Zehan; Péli-Gulli, Marie-Pierre; Gao, Jiegiong; Nishimura, Taki; Eskes, Elja; Stefan, Christopher J.; Winderickx, Joris; Dengjel, Jörn; Ungermann, Christian

doi:10.1016/j.cub.2020.10.026

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Claudio_De_Virgilio_Current_Biology_Vol_31

Journal article

TORC1 Determines Fab1 Lipid Kinase : Function at Signaling Endosomes and Vacuoles : Supplemental Information

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De Virgilio, Claudio University of Fribourg
Chen, Zilei University of Osnabrück
Carpio Malia, Pedro University of Osnabrück
Hatakeyama, Riko University of Fribourg
Nicastro, Raffaele University of Fribourg
Hu, Zehan University of Fribourg
Péli-Gulli, Marie-Pierre University of Fribourg
Gao, Jiegiong University of Osnabrück
Nishimura, Taki University College London
Eskes, Elja Katholieke Universiteit Leuven
Stefan, Christopher J. University College London
Winderickx, Joris Katholieke Universiteit Leuven
Dengjel, Jörn University of Fribourg
Ungermann, Christian University of Osnabrück

05.11.2020

Published in:

Current Biology. - 2021, vol. 31, p. 1-13

TORC1

English Organelles of the endomembrane system maintain their identity and integrity during growth or stress conditions by homeostatic mechanisms that regulate membrane flux and biogenesis. At lysosomes and endosomes, the Fab1 lipid kinase complex and the nutrient-regulated target of rapamycin complex 1 (TORC1) control the integrity of the endolysosomal homeostasis and cellular metabolism. Both complexes are functionally connected as Fab1-dependent generation of PI(3,5)P2 supports TORC1 activity. Here, we identify Fab1 as a target of TORC1 on signaling endosomes, which are distinct from multivesicular bodies, and provide mechanistic insight into their crosstalk. Accordingly, TORC1 can phosphorylate Fab1 proximal to its PI3P-interacting FYVE domain, which causes Fab1 to shift to signaling endosomes, where it generates PI(3,5)P2. This, in turn, regulates (1) vacuole morphology, (2) recruitment of TORC1 and the TORC1-regulatory Rag GTPase-containing EGO complex to signaling endosomes, and (3) TORC1 activity. Thus, our study unravels a regulatory feedback loop between TORC1 and the Fab1 complex that controls signaling at endolysosomes.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

Language

English

Classification

Biological sciences

License

CC BY

Open access status

green

Identifiers

DOI 10.1016/j.cub.2020.10.026

Persistent URL

https://folia.unifr.ch/unifr/documents/312307

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