The I-BAR protein Ivy1 is an effector of the Rab7 GTPase Ypt7 involved in vacuole membrane homeostasis

  • Johannes Numrich
    University of Osnabrück, Department of Biology/Chemistry, Biochemistry section, Barbarastrasse 13, 49076 Osnabrück, Germany
  • Marie-Pierre Péli-Gulli
    University of Fribourg, Department of Biology, Division of Biochemistry, Chemin du Musée 10, Fribourg CH-1700, Switzerland
  • Henning Arlt
    University of Osnabrück, Department of Biology/Chemistry, Biochemistry section, Barbarastrasse 13, 49076 Osnabrück, Germany
  • Alessandro Sardu
    University of Fribourg, Department of Biology, Division of Biochemistry, Chemin du Musée 10, Fribourg CH-1700, Switzerland
  • Janice Griffith
    University Medical Centre Utrecht, Center for Molecular Medicine, Department of Cell Biology, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands
  • Tim Levine
    UCL Institute of Ophthalmology, Department of Cell Biology, 11-43 Bath St., London EC1V 9EL, UK
  • Siegfried Engelbrecht-Vandré
    University of Osnabrück, Department of Biology/Chemistry, Biochemistry section, Barbarastrasse 13, 49076 Osnabrück, Germany
  • Fulvio Reggiori
    University Medical Centre Utrecht, Center for Molecular Medicine, Department of Cell Biology, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands
  • Claudio De Virgilio
    University of Fribourg, Department of Biology, Division of Biochemistry, Chemin du Musée 10, Fribourg CH-1700, Switzerland
  • Christian Ungermann
    University of Osnabrück, Department of Biology/Chemistry, Biochemistry section, Barbarastrasse 13, 49076 Osnabrück, Germany

説明

<jats:title>ABSTRACT</jats:title> <jats:p>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.</jats:p>

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