Loss of BiP/GRP78 function blocks translocation of secretory proteins in yeast.
BiP/GRP78 is an essential member of the HSP70 family that resides in the lumen of the endoplasmic reticulum. In yeast, BiP/GRP78 is encoded by the KAR2 gene. A temperature sensitive mutation was isolated in KAR2 and found to cause a rapid block in protein secretion. Secretory precursors of a number of proteins (invertase, carboxypeptidase Y, alpha-factor, and BiP) accumulated that were characteristic of a block in translocation into the lumen of the ER. Protease protection experiments confirmed that the precursors accumulated on the cytoplasmic side of the ER membrane. Moreover, depletion of wild-type KAR2 protein also resulted in a block in translocation of secretory proteins. These results implicate BiP/GRP78 function in the continued translocation of proteins into the lumen of the ER.
Department of Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08544-1014.
J P
JP
Vogel
L M
LM
Misra
M D
MD
Rose
D000483:Alleles; D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology; D009154:Mutation; D010641:Phenotype; D011233:Precipitin Tests; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013696:Temperature; D014178:Translocation, Genetic / Q000187:drug effects*
D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C060153:KAR2 protein, yeast