Title: | Sorting signals can direct receptor-mediated export of soluble proteins into COPII vesicles |
Address: | "Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA" |
ISSN/ISBN: | 1465-7392 (Print) 1465-7392 (Linking) |
Abstract: | "Soluble secretory proteins are first translocated across endoplasmic reticulum (ER) membranes and folded in a specialized ER luminal environment. Fully folded and assembled secretory cargo are then segregated from ER-resident proteins into COPII-derived vesicles or tubular elements for anterograde transport. Mechanisms of bulk-flow, ER-retention and receptor-mediated export have been suggested to operate during this transport step, although these mechanisms are poorly understood. In yeast, there is evidence to suggest that Erv29p functions as a transmembrane receptor for the export of certain soluble cargo proteins including glycopro-alpha-factor (gpalphaf), the precursor of alpha-factor mating pheromone. Here we identify a hydrophobic signal within the pro-region of gpalphaf that is necessary for efficient packaging into COPII vesicles and for binding to Erv29p. When fused to Kar2p, an ER-resident protein, the pro-region sorting signal was sufficient to direct Erv29p-dependent export of the fusion protein into COPII vesicles. These findings indicate that specific motifs within soluble secretory proteins function in receptor-mediated export from the ER. Moreover, positive sorting signals seem to predominate over potential ER-retention mechanisms that may operate in localizing ER-resident proteins such as Kar2p" |
Keywords: | COP-Coated Vesicles/*metabolism Endoplasmic Reticulum/*metabolism Fungal Proteins/metabolism HSP70 Heat-Shock Proteins/metabolism Mating Factor Membrane Proteins/metabolism Peptides/metabolism Protein Binding/physiology Protein Precursors/metabolism Prote; |
Notes: | "MedlineOtte, Stefan Barlowe, Charles eng Research Support, U.S. Gov't, P.H.S. England 2004/11/02 Nat Cell Biol. 2004 Dec; 6(12):1189-94. doi: 10.1038/ncb1195. Epub 2004 Oct 31" |