Rubicon controls endosome maturation as a Rab7 effector
Open accessAbstract
The activation and recruitment of the small GTPase Rab7 to early endosome is a critical step for early to late endosome maturation, a process that requires the class III phosphatidylinositol 3-kinase (PI3KC3) and GTPase regulators. However, the molecular mechanism underlying Rab7 activation and endosome maturation is still poorly defined. Here we report that Rubicon, a component of the PI3KC3 complex, prevents endosome maturation through differential interactions with Rab7 and UVRAG. UVRAG activates PI3KC3 and C-VPS/HOPS, a guanine nucleotide exchange factor that catalyzes the exchange of GDP for GTP on Rab7. We demonstrate that Rubicon sequesters UVRAG from C-VPS/HOPS. Active GTP-bound Rab7 competes for Rubicon binding and releases UVRAG to associate with C-VPS/HOPS, which in turn promotes further loading of Rab7 with GTP. This feed-forward loop ensures rapid amplification of GTP-bound Rab7 and consequent stimulation of endosome maturation. Hence, Rubicon serves as a previously unknown Rab7 effector to ensure the proper progression of the endocytic pathway.
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Studies in other cell types suggest that Rubicon helps regulate endosome maturation by serving as a RAB7 effector.
“Studies in other cell types suggest that Rubicon helps regulate endosome maturation by serving as a RAB7 effector (Sun et al., 2010).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Sun et al., 2010
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- Authors
- Sun, Q., Westphal, W., Wong, K. N., Tan, I., & Zhong, Q.
- Affiliations
- University of California, Berkeley (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-10-25
- Volume
- 107
- Issue
- 45
- Pages
- 19338-19343
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2984168
- OpenAlex
- W1966828940
- Cited by
- 251
- References
- 37
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 15 · 2023: 15 · 2022: 9 · 2021: 17 · 2020: 12 · 2019: 20 · 2018: 20 · 2017: 24 · 2016: 11 · 2015: 18 · 2014: 14 · 2013: 16 · 2012: 30
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- University of Southern California
- National Institutes of Health
- National Cancer Institute (R01CA133228)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- Rubicon, Rab7, endosome maturation, UVRAG, class III phosphatidylinositol 3-kinase, GTPase activation, guanine nucleotide exchange factor, feed-forward loop, endocytic pathway, early endosomes
- MeSH terms
- Autophagy-Related Proteins, rab7 GTP-Binding Proteins, Carrier Proteins, Endocytosis, Humans, Endosomes, Guanine Nucleotide Exchange Factors, rab GTP-Binding Proteins, Protein Transport, Tumor Suppressor Proteins, Intracellular Signaling Peptides and Proteins, Phosphatidylinositol 3-Kinase
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