AI Article Synopsis
- Researchers identified the YGR198w gene (YPP1) in yeast, which helps reduce the harmful effects of a Parkinson's disease-related alpha-synuclein mutant (A30P).
- YPP1 specifically targets the A30P variant, promoting its transport into vesicles that eventually merge with the vacuole for degradation, while it does not affect the wild-type or another variant (A53T).
- The study further reveals that YPP1 interacts with various genes involved in cellular processes like endocytosis and vesicle trafficking, establishing its crucial role in managing the harmful A30P protein.
Article Abstract
Using a genetic screen we discovered that YGR198w (named YPP1), which is an essential Saccharomyces cerevisiae gene of unknown function, suppresses the toxicity of an alpha-synuclein (alpha-syn) mutant (A30P) that is associated with early onset Parkinson's disease. Here, we show that YPP1 suppresses lethality of A30P, but not of wild-type alpha-syn or the A53T mutant. The Ypp1 protein, when overexpressed, drives each of the three alpha-syns into vesicles that bud off the plasma membrane, but only A30P-containing vesicles traffick to and merge with the vacuole, where A30P is proteolytically degraded. We show that Ypp1p binds to A30P but not the other two alpha-syns; that YPP1 interacts with genes involved in endocytosis/actin dynamics (SLA1, SLA2, and END3), protein sorting (class E vps), and vesicle-vacuole fusion (MON1 and CCZ1) to dispose of A30P; and that YPP1 also participates in pheromone-triggered receptor-mediated endocytosis. Our data reveal that YPP1 mediates the trafficking of A30P to the vacuole via the endocytic pathway.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064368 | PMC |
| http://dx.doi.org/10.1083/jcb.200610071 | DOI Listing |
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