Vac1p coordinates Rab and phosphatidylinositol 3-kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome

Curr Biol. 1999 Feb 11;9(3):159-62. doi: 10.1016/s0960-9822(99)80071-2.

Abstract

The vacuolar protein sorting (VPS) pathway of Saccharomyces cerevisiae mediates transport of vacuolar protein precursors from the late Golgi to the lysosome-like vacuole. Sorting of some vacuolar proteins occurs via a prevacuolar endosomal compartment and mutations in a subset of VPS genes (the class D VPS genes) interfere with the Golgi-to-endosome transport step. Several of the encoded proteins, including Pep12p/Vps6p (an endosomal target (t) SNARE) and Vps45p (a Sec1p homologue), bind each other directly [1]. Another of these proteins, Vac1p/Pep7p/Vps19p, associates with Pep12p and binds phosphatidylinositol 3-phosphate (PI(3)P), the product of the Vps34 phosphatidylinositol 3-kinase (PI 3-kinase) [1] [2]. Here, we demonstrate that Vac1p genetically and physically interacts with the activated, GTP-bound form of Vps21p, a Rab GTPase that functions in Golgi-to-endosome transport, and with Vps45p. These results implicate Vac1p as an effector of Vps21p and as a novel Sec1p-family-binding protein. We suggest that Vac1p functions as a multivalent adaptor protein that ensures the high fidelity of vesicle docking and fusion by integrating both phosphoinositide (Vps34p) and GTPase (Vps21p) signals, which are essential for Pep12p- and Vps45p-dependent targeting of Golgi-derived vesicles to the prevacuolar endosome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins*
  • Endosomes / metabolism*
  • Fungal Proteins / physiology*
  • GTP Phosphohydrolases / physiology*
  • GTP-Binding Proteins / physiology*
  • Golgi Apparatus / metabolism
  • Guanine Nucleotide Dissociation Inhibitors*
  • Guanosine Triphosphate / metabolism
  • Macromolecular Substances
  • Membrane Proteins / physiology
  • Phosphatidylinositol 3-Kinases / physiology*
  • Phosphatidylinositol Phosphates / metabolism
  • Protein Binding
  • Qa-SNARE Proteins
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / ultrastructure
  • Saccharomyces cerevisiae Proteins*
  • Vesicular Transport Proteins*
  • rab GTP-Binding Proteins*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Fungal Proteins
  • GDP dissociation inhibitor 1
  • Guanine Nucleotide Dissociation Inhibitors
  • Macromolecular Substances
  • Membrane Proteins
  • PEP12 protein, S cerevisiae
  • PEP7 protein, S cerevisiae
  • Phosphatidylinositol Phosphates
  • Qa-SNARE Proteins
  • Saccharomyces cerevisiae Proteins
  • VPS45 protein, S cerevisiae
  • Vesicular Transport Proteins
  • phosphatidylinositol 3-phosphate
  • Guanosine Triphosphate
  • Phosphatidylinositol 3-Kinases
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • rab GTP-Binding Proteins