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EMBO J


Title:Brefeldin A reversibly blocks early but not late protein transport steps in the yeast secretory pathway
Author(s):Graham TR; Scott PA; Emr SD;
Address:"Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, La Jolla 92093-0668"
Journal Title:EMBO J
Year:1993
Volume:12
Issue:3
Page Number:869 - 877
DOI: 10.1002/j.1460-2075.1993.tb05727.x
ISSN/ISBN:0261-4189 (Print) 1460-2075 (Electronic) 0261-4189 (Linking)
Abstract:"We have found that brefeldin A (BFA) inhibited the growth of an ise1 mutant of Saccharomyces cerevisiae. Genetic complementation and mapping studies demonstrated that ise1 was allelic to erg6, a gene required for the biosynthesis of the principal membrane sterol of yeast, ergosterol. Treatment of ise1 cells with BFA resulted in an immediate block in protein transport through the secretory pathway. Vacuolar carboxypeptidase Y (CPY) and the secreted pheromone alpha-factor accumulated as both the core glycosylated (ER) and alpha 1,6 mannosylated (early Golgi) forms in drug-treated cells. The modification of alpha-factor with alpha 1,6 mannose in BFA-treated cells did not appear to result from retrograde transport of the alpha 1,6 mannosyl-transferase into the ER. We found that transport of CPY from medial and late Golgi compartments to the vacuole was unaffected by BFA, nor was secretion of alpha 1,3 mannosylated alpha-factor or invertase blocked by BFA. The effects of BFA on the secretory pathway were also reversible after brief exposure (< 40 min) to the drug. We suggest that the primary effect of BFA in S. cerevisiae is restricted to the ER and the alpha 1,6 mannosyltransferase compartment of the Golgi complex"
Keywords:"Biological Transport/drug effects Brefeldin A Carboxypeptidases/metabolism Cathepsin A Cyclopentanes/*pharmacology Endoplasmic Reticulum/metabolism Fungal Proteins/*metabolism Genes, Fungal Genetic Complementation Test Mating Factor Mutation Mycotoxins/*p;"
Notes:"MedlineGraham, T R Scott, P A Emr, S D eng Research Support, Non-U.S. Gov't England 1993/03/01 EMBO J. 1993 Mar; 12(3):869-77. doi: 10.1002/j.1460-2075.1993.tb05727.x"

 
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