Roles for the Drs2p-Cdc50p complex in protein transport and phosphatidylserine asymmetry of the yeast plasma membrane.

Chen S, Wang J, Muthusamy BP, Liu K, Zare S, Andersen RJ, Graham TR
Traffic. 2006 7 (11): 1503-17

PMID: 16956384 · DOI:10.1111/j.1600-0854.2006.00485.x

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.

MeSH Terms (27)

Amino Acid Sequence Annexin A5 Calcium-Transporting ATPases Carboxypeptidases Cathepsin A Cell Membrane Clathrin Heavy Chains Cloning, Molecular Depsipeptides Endocytosis Endoplasmic Reticulum Glycosylation Golgi Apparatus Mating Factor Molecular Sequence Data Mutation Peptides Peptides, Cyclic Phosphatidylserines Phospholipids Proprotein Convertases Protein Binding Protein Transport Recombinant Fusion Proteins Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Sequence Homology, Amino Acid

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