title: Membrane transport in Caenorhabditis elegans: an essential role for VPS34 at the nuclear membrane.
abstract: Here we present a detailed genetic analysis of let-512/vps34 that encodes the Caenorhabditis elegans homologue of the yeast phosphatidylinositol 3-kinase Vps34p. LET-512/VPS34 has essential functions and is ubiquitously expressed in all tissues and developmental stages. It accumulates at a perinuclear region, and mutations in let-512/vps34 result in an expansion of the outer nuclear membrane as well as in a mislocalization and subsequent complete lack of expression of LRP-1, a C.elegans LDL receptor normally associated with the apical surface of hypodermal cells. Using a GFP::2xFYVE fusion protein we found that the phosphatidylinositol 3-phosphate (PtdIns 3-P) product of LET-512/VPS34 is associated with a multitude of intracellular membranes and vesicles located at the periphery, including endocytic vesicles. We propose that LET-512/VPS34 is required for membrane transport from the outer nuclear membrane towards the cell periphery. Thus, LET-512/VPS34 may regulate the secretory pathway in a much broader range of compartments than was previously suggested for the yeast orthologue.
authors.affiliation: Department of Biology, University of Fribourg, CH-1700 Fribourg, Switzerland.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Roggo
authors.forename: Vincent
authors.initials: V
authors.lastname: Bernard
authors.forename: Attila L
authors.initials: AL
authors.lastname: Kovacs
authors.forename: Ann M
authors.initials: AM
authors.lastname: Rose
authors.forename: Fabienne
authors.initials: F
authors.lastname: Savoy
authors.forename: Monique
authors.initials: M
authors.lastname: Zetka
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Wymann
authors.forename: Fritz
authors.initials: F
authors.lastname: Müller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D015870:Gene Expression; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009685:Nuclear Envelope / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D019869:Phosphatidylinositol 3-Kinases