Open AccessIvy1 is a negative regulator of Gtr-dependent TORC1 activation
Author(s) -
Natalia V. Varlakhanova,
Bryan A. Tornabene,
M.G.J. Ford
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.218305
Subject(s) - biology , regulator , negative regulator , microbiology and biotechnology , genetics , signal transduction , gene
The highly conserved TORC1 complex controls cell growth in response to nutrients, especially amino acids. EGO Complex activates TORC1 in response to glutamine and leucine. Here, we demonstrate that the I-BAR domain-containing protein Ivy1 colocalizes with Gtr1 and Gtr2, a heterodimer of small GTPases that are part of EGO Complex. Ivy1 is a negative regulator of Gtr-induced TORC1 activation. Ivy1 is contained within puncta associated with the vacuolar membrane in cells grown in rich medium or after brief nitrogen starvation. Addition of glutamine to nitrogen-starved cells leads to dissipation of Ivy1 puncta and redistribution of Ivy1 throughout the vacuolar membrane. Continued stimulation with glutamine results in concentration of Ivy1 within vacuolar membrane invaginations and its spatial separation from EGO Complex components Gtr1 and Gtr2. Disruption of vacuolar membrane invagination is associated with persistent mislocalization of Ivy1 across the vacuolar membrane and inhibition of TORC1 activity. Together, our findings illustrate a novel negative feedback pathway exerted by Ivy1 on Gtr-dependent TORC1 signaling and provide insight into a potential molecular mechanism underlying TORC1 activation by vacuolar membrane remodeling.