Remodeling the Specificity of an Endosomal CORVET Tether Underlies Formation of Regulated Secretory Vesicles in the Ciliate Tetrahymena thermophila

Current Biology : CB
Daniela SparvoliAaron P Turkewitz

Abstract

In the endocytic pathway of animals, two related complexes, called CORVET (class C core vacuole/endosome transport) and HOPS (homotypic fusion and protein sorting), act as both tethers and fusion factors for early and late endosomes, respectively. Mutations in CORVET or HOPS lead to trafficking defects and contribute to human disease, including immune dysfunction. HOPS and CORVET are conserved throughout eukaryotes, but remarkably, in the ciliate Tetrahymena thermophila, the HOPS-specific subunits are absent, while CORVET-specific subunits have proliferated. VPS8 (vacuolar protein sorting), a CORVET subunit, expanded to 6 paralogs in Tetrahymena. This expansion correlated with loss of HOPS within a ciliate subgroup, including the Oligohymenophorea, which contains Tetrahymena. As uncovered via forward genetics, a single VPS8 paralog in Tetrahymena (VPS8A) is required to synthesize prominent secretory granules called mucocysts. More specifically, Δvps8a cells fail to deliver a subset of cargo proteins to developing mucocysts, instead accumulating that cargo in vesicles also bearing the mucocyst-sorting receptor Sor4p. Surprisingly, although this transport step relies on CORVET, it does not appear to involve early endosomes. Inste...Continue Reading

Citations

Feb 12, 2020·The Journal of Cell Biology·Cheng-I J MaJulie A Brill
Jan 23, 2020·Journal of Cell Science·Daniela SparvoliAaron P Turkewitz
May 30, 2019·Molecular Biology of the Cell·Shweta V PipaliyaJoel Dacks
Oct 29, 2020·Molecular Biology of the Cell·Jason C CaslerBenjamin S Glick
May 20, 2020·Current Biology : CB·Kira MoreJoel B Dacks
Apr 19, 2021·Advances in Biological Regulation·Cheng-I Jonathan MaJulie A Brill
May 29, 2021·Trends in Parasitology·Daniela Sparvoli, Maryse Lebrun

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