Distinct roles of the two <scp>VPS33</scp> proteins in the endolysosomal system in <i>Caenorhabditis elegans</i>

<jats:p>Sec1/Munc‐18 (<jats:styled-content style="fixed-case">SM</jats:styled-content>) family proteins are essential regulators in intracellular transport in eukaryotic cells. The <jats:styled-content style="fixed-case">SM</jats:styled-content> 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, <jats:styled-content style="fixed-case">VPS33A</jats:styled-content> and <jats:styled-content style="fixed-case">VPS33B</jats:styled-content>, but their precise roles remain unknown. Here, we present a comparative analysis of <jats:italic>Caenorhabditis elegans</jats:italic> null mutants for these proteins. We found that the <jats:italic>vps‐33.1</jats:italic> (<jats:styled-content style="fixed-case">VPS33A</jats:styled-content>) mutants exhibited severe defects in both endocytic function and endolysosomal biogenesis in scavenger cells. Furthermore, <jats:italic>vps‐33.1</jats:italic> mutations caused endocytosis defects in other tissues, and the loss of maternal and zygotic <jats:styled-content style="fixed-case">VPS</jats:styled-content>‐33.1 resulted in embryonic lethality. By contrast, <jats:italic>vps‐33.2</jats:italic> mutants were viable but sterile, with terminally arrested spermatocytes. The spermatogenesis phenotype suggests that <jats:styled-content style="fixed-case">VPS33</jats:styled-content>.2 is involved in the formation of a sperm‐specific organelle. The endocytosis defect in the <jats:italic>vps‐33.1</jats:italic> mutant was not restored by the expression of <jats:styled-content style="fixed-case">VPS</jats:styled-content>‐33.2, which indicates that these proteins have nonredundant functions. Together, our data suggest that <jats:styled-content style="fixed-case">VPS</jats:styled-content>‐33.1 shares most of the general functions of yeast Vps33 in terms of tethering complexes in the endolysosomal system, whereas <jats:styled-content style="fixed-case">VPS</jats:styled-content>‐33.2 has tissue/organelle specific functions in <jats:italic>C. elegans</jats:italic>.</jats:p><jats:p><jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tra12430-gra-0001.png" xlink:title="image" /></jats:p>