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

• Published in: Current biology 1999-02, Vol.9 (3), p.159,S1-162,S1
• Main Authors: Peterson, Michael R., Burd, Christopher G., Emr, Scott D.
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Cytoskeletal Proteins; Endosomes - metabolism; Fungal Proteins - physiology; Golgi Apparatus - metabolism; GTP Phosphohydrolases - physiology; GTP-Binding Proteins - physiology; Guanine Nucleotide Dissociation Inhibitors; Guanosine Triphosphate - metabolism; Macromolecular Substances; Membrane Proteins - physiology; Phosphatidylinositol 3-Kinases - physiology; Phosphatidylinositol Phosphates - metabolism; Protein Binding; Qa-SNARE Proteins; rab GTP-Binding Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - ultrastructure; Saccharomyces cerevisiae Proteins; Vesicular Transport Proteins
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/S0960-9822(99)80071-2

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.