title: Distinct roles of the two VPS33 proteins in the endolysosomal system in Caenorhabditis elegans.
abstract: Sec1/Munc-18 (SM) family proteins are essential regulators in intracellular transport in eukaryotic cells. The SM protein Vps33 functions as a core subunit of two tethering complexes, class C core vacuole/endosome tethering (CORVET) and homotypic fusion and vacuole protein sorting (HOPS) in the endocytic pathway in yeast. Metazoan cells possess two Vps33 proteins, VPS33A and VPS33B, but their precise roles remain unknown. Here, we present a comparative analysis of Caenorhabditis elegans null mutants for these proteins. We found that the vps-33.1 (VPS33A) mutants exhibited severe defects in both endocytic function and endolysosomal biogenesis in scavenger cells. Furthermore, vps-33.1 mutations caused endocytosis defects in other tissues, and the loss of maternal and zygotic VPS-33.1 resulted in embryonic lethality. By contrast, vps-33.2 mutants were viable but sterile, with terminally arrested spermatocytes. The spermatogenesis phenotype suggests that VPS33.2 is involved in the formation of a sperm-specific organelle. The endocytosis defect in the vps-33.1 mutant was not restored by the expression of VPS-33.2, which indicates that these proteins have nonredundant functions. Together, our data suggest that VPS-33.1 shares most of the general functions of yeast Vps33 in terms of tethering complexes in the endolysosomal system, whereas VPS-33.2 has tissue/organelle specific functions in C. elegans.
authors: Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. andok@mail.saitama-u.ac.jp.|Brain and Body System Science Institute, Saitama University, Saitama, Japan. andok@mail.saitama-u.ac.jp.|Graduate School of Science and Engineering, Saitama University, Saitama, Japan. andok@mail.saitama-u.ac.jp.
authors: Keiko
authors: K
authors: Gengyo-Ando
authors: Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.|The OCU Advanced Research Institute for Natural Science and Technology, Osaka City University, Osaka, Japan.
authors: Eriko
authors: E
authors: Kage-Nakadai
authors: Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
authors: Sawako
authors: S
authors: Yoshina
authors: Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
authors: Muneyoshi
authors: M
authors: Otori
authors: Brain and Body System Science Institute, Saitama University, Saitama, Japan.|Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
authors: Yuko
authors: Y
authors: Kagawa-Nagamura
authors: Brain and Body System Science Institute, Saitama University, Saitama, Japan.|Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
authors: Junichi
authors: J
authors: Nakai
authors: Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. mitani.shohei@twmu.ac.jp.
authors: Shohei
authors: S
authors: Mitani
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics / Q000502:physiology*; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D009154:Mutation; D009865:Oocytes / Q000378:metabolism / Q000648:ultrastructure; D021381:Protein Transport; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D013094:Spermatozoa / Q000378:metabolism / Q000648:ultrastructure; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C000599723:VPS-33.1 protein, C elegans; C000599722:VPS-33.2 protein, C elegans; D033921:Vesicular Transport Proteins
keywords: Caenorhabditis elegans; VPS-33.1; VPS-33.2; endocytosis; spermatogenesis