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J Cell Biol

Title:		YGR198w (YPP1) targets A30P alpha-synuclein to the vacuole for degradation
Author(s):		Flower TR; Clark-Dixon C; Metoyer C; Yang H; Shi R; Zhang Z; Witt SN;
Address:		"Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA"
Journal Title:		J Cell Biol
Year:		2007
Volume:		177
Issue:		6
Page Number:		1091 - 1104
DOI:		10.1083/jcb.200610071
ISSN/ISBN:		0021-9525 (Print) 1540-8140 (Electronic) 0021-9525 (Linking)
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"
Keywords:		"Adaptor Proteins, Vesicular Transport/*metabolism Carrier Proteins/*metabolism Endocytosis Parkinson Disease Peptide Hydrolases/metabolism Protein Transport Saccharomyces cerevisiae Proteins/*metabolism Vacuoles/*metabolism alpha-Synuclein/*metabolism;"
Notes:		"MedlineFlower, Todd R Clark-Dixon, Cheryl Metoyer, Cheynita Yang, Hui Shi, Runhua Zhang, Zhaojie Witt, Stephan N eng R21 NS053678/NS/NINDS NIH HHS/ R21NS053678/NS/NINDS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2007/06/20 J Cell Biol. 2007 Jun 18; 177(6):1091-104. doi: 10.1083/jcb.200610071"