The Vam6 GEF controls TORC1 by activating the EGO complex

Binda, Matteo; Péli-Gulli, Marie-Pierre; Bonfils, Grégory; Panchaud, Nicolas; Urban, Jörg; Sturgill, Thomas W.; Loewith, Robbie; De Virgilio, Claudio

doi:10.1016/j.molcel.2009.06.033

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The Vam6 GEF controls TORC1 by activating the EGO complex

Binda, Matteo Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
Péli-Gulli, Marie-Pierre Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
Bonfils, Grégory Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
Panchaud, Nicolas Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland
Urban, Jörg Department of Molecular Biology, University of Geneva, Switzerland
Sturgill, Thomas W. Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville, USA
Loewith, Robbie Department of Molecular Biology, University of Geneva, Switzerland
De Virgilio, Claudio Division of Biochemistry, Department of Medicine, University of Fribourg, Switzerland

11.09.2009

Published in:

Molecular Cell. - 2009, vol. 35, no. 5, p. 563-573

English The target of rapamycin complex 1 (TORC1) is a central regulator of eukaryotic cell growth that is activated by a variety of hormones (e.g., insulin) and nutrients (e.g., amino acids) and is deregulated in various cancers. Here, we report that the yeast Rag GTPase homolog Gtr1, a component of the vacuolar-membrane-associated EGO complex (EGOC), interacts with and activates TORC1 in an amino-acid-sensitive manner. Expression of a constitutively active (GTP-bound) Gtr1^GTP, which interacted strongly with TORC1, rendered TORC1 partially resistant to leucine deprivation, whereas expression of a growth inhibitory, GDP-bound Gtr1^GDP, caused constitutively low TORC1 activity. We also show that the nucleotide-binding status of Gtr1 is regulated by the conserved guanine nucleotide exchange factor (GEF) Vam6. Thus, in addition to its regulatory role in homotypic vacuolar fusion and vacuole protein sorting within the HOPS complex, Vam6 also controls TORC1 function by activating the Gtr1 subunit of the EGO complex.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

Language

English

Classification

Biological sciences

License

License undefined

Identifiers

RERO DOC 13185
DOI 10.1016/j.molcel.2009.06.033

Persistent URL

https://folia.unifr.ch/unifr/documents/301365

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