Interaction between VPS35 and RABG3f is necessary as a checkpoint to control fusion of late compartments with the vacuole

Journal Article · 30 September 2019 · Proceedings of the National Academy of Sciences of the United States of America

DOI: https://doi.org/10.1073/pnas.1905321116 · OSTI ID:1567871

Rodriguez-Furlan, Cecilia  ^[1]; Domozych, David ^[2]; Qian, Weixing ^[3]; Enquist, Per-Anders ^[3]; Li, Xiaohui  ^[4]; Zhang, Chunhua  ^[4]; Schenk, Rolf ^[1]; Winbigler, Holly Saulsbery ^[5]; Jackson, William ^[5]; Raikhel, Natasha V. ^[1]; Hicks, Glenn R. ^[6]

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1. Department of Botany and Plant Sciences, University of California, Riverside, CA 92506,, Institute of Integrative Genome Biology, University of California, Riverside, CA 92506,
2. Biology Department, Skidmore College, Saratoga Springs, NY 12866,
3. Department of Chemistry, Umea University, SE-901 87 Umea, Sweden,, Department of Chemistry, Chemical Biology Consortium Sweden, SE-901 87 Umea, Sweden,
4. Department of Botany and Plant Pathology, Purdue University, West Lafayette, IN 47906,, Center for Plant Biology, Purdue University, West Lafayette, IN 47906,
5. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 20201,
6. Department of Botany and Plant Sciences, University of California, Riverside, CA 92506,, Institute of Integrative Genome Biology, University of California, Riverside, CA 92506,, Uppsala BioCenter, Swedish University of Agricultural Sciences, SE-75007 Uppsala, Sweden

Significance In plants, the retromer complex (VPS35, VPS29, VPS26) has been implicated in retrograde traffic from the endosomes back to the trans -Golgi network. Nevertheless, vps35 mutants exhibit impaired anterograde traffic toward the vacuole (synthetic, endocytic, and autophagic). This paradox remains an open question. We show that the small molecule endosidin17 (ES17) targets VPS35, which disrupts its association with RABG3f. This, in turn, impairs retromer complex membrane anchoring, producing vps35 mutant-like phenotypes. Using ES17, we found that VPS35–RABG3f binding precedes the release of RABG3f–GTP to interact with the vacuolar homotypic fusion and vacuole protein sorting (HOPS) complex, which is required for fusion of late compartments with the tonoplast. Thus, VPS35–RABG3f interaction constitutes a checkpoint before proceeding with membrane fusion.

• Sponsoring Organization: USDOE Office of Science (SC), Basic Energy Sciences (BES)
• OSTI ID: 1567871
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 42 Vol. 116; ISSN 0027-8424
• Publisher: Proceedings of the National Academy of SciencesCopyright Statement
• Country of Publication: United States
• Language: English