title: Loss of the Sec1/Munc18-family proteins VPS-33.2 and VPS-33.1 bypasses a block in endosome maturation in Caenorhabditis elegans.
abstract: The end of the life of a transport vesicle requires a complex series of tethering, docking, and fusion events. Tethering complexes play a crucial role in the recognition of membrane entities and bringing them into close opposition, thereby coordinating and controlling cellular trafficking events. Here we provide a comprehensive RNA interference analysis of the CORVET and HOPS tethering complexes in metazoans. Knockdown of CORVET components promoted RAB-7 recruitment to subapical membranes, whereas in HOPS knockdowns, RAB-5 was found also on membrane structures close to the cell center, indicating the RAB conversion might be impaired in the absence of these tethering complexes. Unlike in yeast, metazoans have two VPS33 homologues, which are Sec1/Munc18 (SM)-family proteins involved in the regulation of membrane fusion. We assume that in wild type, each tethering complex contains a specific SM protein but that they may be able to substitute for each other in case of absence of the other. Of importance, knockdown of both SM proteins allowed bypass of the endosome maturation block in sand-1 mutants. We propose a model in which the SM proteins in tethering complexes are required for coordinated flux of material through the endosomal system.
authors.affiliation: Growth and Development, Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Jachen A
authors.initials: JA
authors.lastname: Solinger
authors.affiliation: Growth and Development, Biozentrum, University of Basel, CH-4056 Basel, Switzerland anne.spang@unibas.ch.
authors.forename: Anne
authors.initials: A
authors.lastname: Spang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics; D011992:Endosomes / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008561:Membrane Fusion; D008856:Microscopy, Fluorescence; D051938:Munc18 Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D034622:RNA Interference; D022161:Transport Vesicles / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D029742:Caenorhabditis elegans Proteins; D051938:Munc18 Proteins; C506114:SAND-1 protein, C elegans; C000599723:VPS-33.1 protein, C elegans; C000599722:VPS-33.2 protein, C elegans; D033921:Vesicular Transport Proteins; D000090802:rab7 GTP-Binding Proteins; D049452:Green Fluorescent Proteins; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins