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Traffic

Title:		Roles for the Drs2p-Cdc50p complex in protein transport and phosphatidylserine asymmetry of the yeast plasma membrane
Author(s):		Chen S; Wang J; Muthusamy BP; Liu K; Zare S; Andersen RJ; Graham TR;
Address:		"Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA"
Journal Title:		Traffic
Year:		2006
Volume:		20060901
Issue:		11
Page Number:		1503 - 1517
DOI:		10.1111/j.1600-0854.2006.00485.x
ISSN/ISBN:		1398-9219 (Print) 1398-9219 (Linking)
Abstract:		"Drs2p, a P-type adenosine triphosphatase required for a phosphatidylserine (PS) flippase activity in the yeast trans Golgi network (TGN), was first implicated in protein trafficking by a screen for mutations synthetically lethal with arf1 (swa). Here, we show that SWA4 is allelic to CDC50, encoding a membrane protein previously shown to chaperone Drs2p from the endoplasmic reticulum to the Golgi complex. We find that cdc50Delta exhibits the same clathrin-deficient phenotypes as drs2Delta, including delayed transport of carboxypeptidase Y to the vacuole, mislocalization of resident TGN enzymes and the accumulation of aberrant membrane structures. These trafficking defects precede appearance of cell polarity defects in cdc50Delta, suggesting that the latter are a secondary consequence of disrupting Golgi function. Involvement of Drs2p-Cdc50p in PS translocation suggests a role in restricting PS to the cytosolic leaflet of the Golgi and plasma membrane. Annexin V binding and papuamide B hypersensitivity indicate that drs2Delta or cdc50Delta causes a loss of plasma membrane PS asymmetry. However, clathrin and other endocytosis null mutants also exhibit a comparable loss of PS asymmetry, and studies with drs2-ts and clathrin (chc1-ts) conditional mutants suggest that loss of plasma membrane asymmetry is a secondary consequence of disrupting protein trafficking"
Keywords:		"Amino Acid Sequence Annexin A5/metabolism Calcium-Transporting ATPases/genetics/metabolism/*physiology Carboxypeptidases/genetics/metabolism Cathepsin A Cell Membrane/*metabolism Clathrin Heavy Chains/genetics/metabolism Cloning, Molecular Depsipeptides/p;"
Notes:		"MedlineChen, Sophie Wang, Jiyi Muthusamy, Baby-Periyanayaki Liu, Ke Zare, Sara Andersen, Raymond J Graham, Todd R eng GM62367/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural England 2006/09/08 Traffic. 2006 Nov; 7(11):1503-17. doi: 10.1111/j.1600-0854.2006.00485.x. Epub 2006 Sep 1"