Ergosterol is required for targeting of tryptophan permease to the yeast plasma membrane
Open accessAbstract
It was known that the uptake of tryptophan is reduced in the yeast erg6 mutant, which is defective in a late step of ergosterol biosynthesis. Here, we show that this is because the high affinity tryptophan permease Tat2p is not targeted to the plasma membrane. In wild-type cells, the plasma membrane localization of Tat2p is regulated by the external tryptophan concentration. Tat2p is transported from the Golgi apparatus to the vacuole at high tryptophan, and to the plasma membrane at low tryptophan. However, in the erg6 mutant, Tat2p is missorted to the vacuole at low tryptophan. The plasma membrane targeting of Tat2p is dependent on detergent-insoluble membrane domains, suggesting that sterol affects the sorting through the organization of lipid rafts. The erg6 mutation also caused missorting to the multivesicular body pathway in late endosomes. Thus, sterol composition is crucial for protein sorting late in the secretory pathway. Tat2p is subject to polyubiquitination, which acts as a vacuolar-targeting signal, and the inhibition of this process suppresses the Tat2p sorting defects of the erg6 mutant. The sorting mechanisms of Tat2p that depend on both sterol and ubiquitin will be discussed.
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Ergosterol enriched in lipid rafts is implicated in sporulation, pheromone signaling, polarization and membrane fusion during mating and endocytosis in S. cerevisiae.
“In addition, ergosterol enriched in lipid rafts has been implicated in many cellular processes, such as sporulation, pheromone signaling, polarization and membrane fusion during mating and endocytosis in S. cerevisiae .”
From The synthesis, regulation, and functions of sterols in<i>Candida albicans</i>: Well-known but still lots to learn (2016) · cites this paper as [69]
The Introduction (page unavailable) says sterol composition affects endocytosis in yeast and that lipid rafts are important for protein sorting. The Discussion (page unavailable) suggests impaired raft association may explain a mating deficiency in an ergosterol-biosynthesis mutant. The paper does not substantiate the full list: sporulation, pheromone signaling, and membrane fusion during mating are not addressed, and polarization appears only in a cited reference title. (LLM, conf=0.85)
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- Authors
- Umebayashi, K., & Nakano, A.
- Affiliations
- RIKEN (JP)
- Corresponding author
- Nakano, Akihiko
- ORCID
- Nakano, Akihiko
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2003-06-16
- Volume
- 161
- Issue
- 6
- Pages
- 1117-1131
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2172991
- OpenAlex
- W2156681354
- Cited by
- 230
- References
- 56
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 13 · 2019: 10 · 2018: 6 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 5 · 2013: 8 · 2012: 11
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- ergosterol, plasma membrane targeting, protein sorting, sterol biosynthesis, lipid rafts, vacuoles, multivesicular bodies, late endosomes, polyubiquitination, vacuolar targeting, secretory pathway, yeast
- MeSH terms
- Cell Membrane, Cells, Cultured, Ergosterol, Mutation, Endosomes, Saccharomyces cerevisiae, Tryptophan, Vacuoles, Protein Structure, Tertiary, Protein Transport, Membrane Microdomains, Transport Vesicles, Ubiquitin, Amino Acid Transport Systems, Saccharomyces cerevisiae Proteins
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