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Curr Biol. 2018 Mar 5;28(5):697-710.e13. doi: 10.1016/j.cub.2018.01.047. Epub 2018 Feb 22.

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

Author information

1
Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL, USA.
2
Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2R3, Canada.
3
Advanced ICT Research Institute, National Institute of Information and Communications Technology (NICT), Kobe 651-2492, Japan.
4
Department of Genetics, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
5
Department of Biological Sciences, Boise State University, Boise, ID 83725-1515, USA.
6
Department of Integrative Biology, University of Guelph, Guelph, ON N1G 2W1, Canada.
7
Department of Genetics, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA.
8
Advanced ICT Research Institute, National Institute of Information and Communications Technology (NICT), Kobe 651-2492, Japan; Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan.
9
Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL, USA. Electronic address: apturkew@uchicago.edu.

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. Instead, Vps8a associates with the late endosomal/lysosomal marker Rab7, indicating that target specificity switching occurred in CORVET subunits during the evolution of ciliates. Mucocysts belong to a markedly diverse and understudied class of protist secretory organelles called extrusomes. Our results underscore that biogenesis of mucocysts depends on endolysosomal trafficking, revealing parallels with invasive organelles in apicomplexan parasites and suggesting that a wide array of secretory adaptations in protists, like in animals, depend on mechanisms related to lysosome biogenesis.

KEYWORDS:

alveolata; endosomal tether; evolution; extrusome; gene loss; lysosome-related organelle; membrane trafficking; protist

PMID:
29478853
PMCID:
PMC5840023
[Available on 2019-03-05]
DOI:
10.1016/j.cub.2018.01.047

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