Loss of BiP/GRP78 function blocks translocation of secretory proteins in yeast

doi:10.1083/jcb.110.6.1885

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Loss of BiP/GRP78 function blocks translocation of secretory proteins in yeast

JP Vogel, LM Misra and MD Rose
Department of Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08544-1014.

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.
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