Fab1p PtdIns(3)P 5-Kinase Function Essential for Protein Sorting in the Multivesicular Body
Open accessAbstract
Sorting of signal-transducing cell surface receptors within multivesicular bodies (MVBs) is required for their rapid down-regulation and degradation within lysosomes. Yeast mutants defective in late stages of transport to the vacuole/lysosome accumulate MVBs. We demonstrate that the membrane glycoprotein carboxypeptidase S and the G protein-coupled receptor Ste2p are targeted into the vacuole lumen, and this process requires a subset of VPS gene products essential for normal endosome function. The PtdIns(3)P 5-kinase activity of Fab1p, which converts the product of the Vps34p PtdIns 3-kinase PtdIns(3)P into PtdIns(3,5)P2, also is required for cargo-selective sorting into the vacuole lumen. These findings demonstrate a role for phosphoinositide signaling at distinct stages of vacuolar/lysosomal protein transport and couple PtdIns(3,5)P2 synthesis to regulation of MVB sorting.
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ILV formation requires two distinct processes: organization of the endosome membrane into tetraspanin-enriched microdomains (TEMs) and ESCRT complexes.
“Work in yeast [28-31] and other tissue culture models [32-34] suggests that ILV formation requires two distinct processes. The first involves the organization of the endosome membrane into specialized units highly enriched for a class of membrane proteins called tetraspanins [35].”
From Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies (2013) · cites this paper as [28]
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Self-citation
- Authors
- Odorizzi, G., Babst, M., & Emr, S. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Emr, Scott D
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1998-12
- Volume
- 95
- Issue
- 6
- Pages
- 847-858
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1965476757
- Cited by
- 656
- References
- 1
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 9 · 2022: 5 · 2021: 23 · 2020: 13 · 2019: 11 · 2018: 12 · 2017: 19 · 2016: 8 · 2015: 20 · 2014: 12 · 2013: 31 · 2012: 25
- FWCI
- 14.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ca058689-10)
- National Cancer Institute (CA 58689)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- multivesicular bodies, protein sorting, Ste2p, G protein-coupled receptors, PtdIns(3,5)P2, phosphoinositide signaling, lysosomal protein degradation, receptor down-regulation, yeast
- MeSH terms
- Adenosine Triphosphatases, Biological Transport, Carboxypeptidases, Fungal Proteins, Luminescent Proteins, Endosomes, Recombinant Fusion Proteins, Vacuoles, Phosphotransferases (Alcohol Group Acceptor), Saccharomyces cerevisiae Proteins, Green Fluorescent Proteins, Endosomal Sorting Complexes Required for Transport
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