title: The I-BAR protein Ivy1 is an effector of the Rab7 GTPase Ypt7 involved in vacuole membrane homeostasis.
abstract: Membrane fusion at the vacuole depends on a conserved machinery that includes SNAREs, the Rab7 homolog Ypt7 and its effector HOPS. Here, we demonstrate that Ypt7 has an unexpected additional function by controlling membrane homeostasis and nutrient-dependent signaling on the vacuole surface. We show that Ivy1, the yeast homolog of mammalian missing-in-metastasis (MIM), is a vacuolar effector of Ypt7-GTP and interacts with the EGO/ragulator complex, an activator of the target of rapamycin kinase complex 1 (TORC1) on vacuoles. Loss of Ivy1 does not affect EGO vacuolar localization and function. In combination with the deletion of individual subunits of the V-ATPase, however, we observed reduced TORC1 activity and massive enlargement of the vacuole surface. Consistent with this, Ivy1 localizes to invaginations at the vacuole surface and on liposomes in a phosphoinositide- and Ypt7-GTP-controlled manner, which suggests a role in microautophagy. Our data, thus, reveal that Ivy1 is a novel regulator of vacuole membrane homeostasis with connections to TORC1 signaling.
authors.affiliation: University of Osnabrück, Department of Biology/Chemistry, Biochemistry section, Barbarastrasse 13, 49076 Osnabrück, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Numrich
authors.affiliation: University of Fribourg, Department of Biology, Division of Biochemistry, Chemin du Musée 10, Fribourg CH-1700, Switzerland.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Péli-Gulli
authors.affiliation: University of Osnabrück, Department of Biology/Chemistry, Biochemistry section, Barbarastrasse 13, 49076 Osnabrück, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Arlt
authors.affiliation: University of Fribourg, Department of Biology, Division of Biochemistry, Chemin du Musée 10, Fribourg CH-1700, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sardu
authors.affiliation: University Medical Centre Utrecht, Center for Molecular Medicine, Department of Cell Biology, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands.
authors.forename: Janice
authors.initials: J
authors.lastname: Griffith
authors.affiliation: UCL Institute of Ophthalmology, Department of Cell Biology, 11-43 Bath St., London EC1V 9EL, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Levine
authors.affiliation: University of Osnabrück, Department of Biology/Chemistry, Biochemistry section, Barbarastrasse 13, 49076 Osnabrück, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Engelbrecht-Vandré
authors.affiliation: University Medical Centre Utrecht, Center for Molecular Medicine, Department of Cell Biology, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Reggiori
authors.affiliation: University of Fribourg, Department of Biology, Division of Biochemistry, Chemin du Musée 10, Fribourg CH-1700, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: De Virgilio
authors.affiliation: University of Osnabrück, Department of Biology/Chemistry, Biochemistry section, Barbarastrasse 13, 49076 Osnabrück, Germany cu@uos.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Ungermann
mesh_terms: D001343:Autophagy; D002352:Carrier Proteins / Q000378:metabolism*; D004705:Endocytosis; D006706:Homeostasis; D007425:Intracellular Membranes / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D008954:Models, Biological; D046912:Multiprotein Complexes; D010716:Phosphatidylinositols / Q000378:metabolism; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014617:Vacuoles / Q000378:metabolism* / Q000648:ultrastructure; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C475841:IVY1 protein, S cerevisiae; D046912:Multiprotein Complexes; D010716:Phosphatidylinositols; D029701:Saccharomyces cerevisiae Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; C079005:YPT7 protein, S cerevisiae; D020691:rab GTP-Binding Proteins
keywords: EGO complex; Ivy1; TORC1; Vacuole biogenesis; Vps33; Ypt7