title: Novel pathways, membrane coats and PI kinase regulation in yeast lysosomal trafficking.
abstract: Analysis of membrane transport in the yeast Saccharomyces cerevisiae continues to provide important insights into the molecular mechanisms that direct endocytic and lysosomal sorting pathways in eukaryotic cells. Recent findings include the identification of two novel endomembrane transport pathways, a Golgi-to-vacuole biosynthetic pathway requiring the adaptor protein-3 (AP-3) complex, and a vacuolar membrane recycling pathway regulated by PtdIns(3,5)P2. At the molecular level, a candidate vesicle coat protein complex mediating endosome-to-Golgi recycling has been identified. In addition, protein sorting signals directing phosphorylation-dependent ubiquitination of endocytic cargoes, and a recognition motif for AP-3-dependent sorting have been characterized. Important mechanistic insights into SNARE-mediated, NSF-dependent membrane fusion reactions also have been made using yeast-based in vitro assays and the identification of the zinc-binding FYVE domain as a PtdIns(3)P-specific binding domain has linked phosphoinositide signaling to the regulation of vesicle docking/fusion, as well as other membrane transport reactions along the lysosomal sorting pathways.
authors.affiliation: University of California, San Diego, School of Medicine and Howard Hughes Medical Institute, 9500 Gilman Drive, La Jolla, CA, 92093-0668, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Burd
authors.forename: M
authors.initials: M
authors.lastname: Babst
authors.forename: S D
authors.initials: SD
authors.lastname: Emr
mesh_terms: D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000469:Alkaline Phosphatase / Q000378:metabolism; D001692:Biological Transport; D002268:Carboxypeptidases / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology; D043402:Cathepsin A; D002462:Cell Membrane / Q000378:metabolism*; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D005656:Fungal Proteins / Q000502:physiology*; D007425:Intracellular Membranes / Q000502:physiology; D008247:Lysosomes / Q000201:enzymology / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D008954:Models, Biological; D034041:Monomeric Clathrin Assembly Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000502:physiology* / Q000648:ultrastructure; D014617:Vacuoles / Q000201:enzymology / Q000502:physiology*
chemical_list: D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000469:Alkaline Phosphatase; D002268:Carboxypeptidases; D002352:Carrier Proteins; D043402:Cathepsin A; D005656:Fungal Proteins; D008565:Membrane Proteins; D034041:Monomeric Clathrin Assembly Proteins; D019869:Phosphatidylinositol 3-Kinases; C439023:clathrin assembly protein AP180