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Sorting signals can direct receptor-mediated export of soluble proteins into COPII vesicles

Nature Cell Biology volume 6, pages 1189–1194 (2004)Cite this article

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 understood1,2,3,4,5,6,7. In yeast, there is evidence to suggest that Erv29p functions as a transmembrane receptor for the export of certain soluble cargo proteins including glycopro-α-factor (gpαf), the precursor of α-factor mating pheromone8. Here we identify a hydrophobic signal within the pro-region of gpαf 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.

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Figure 1: Hydrophobic residues within the pro-region are required for efficient packaging of gpαf.
Figure 2: The I-L-V motif is required for the binding of gpαf to Erv29p.
Figure 3: The ppαf–Kar2p fusion proteins are specifically sorted into COPII vesicles.
Figure 4: The I-L-V motif influences distribution of ppαf–Kar2p in vivo.

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Acknowledgements

We thank E. Harris and Y. Jun for their assistance in the early stages of this study and T. Stevens for providing anti-Pdi1p serum. We also thank J. Flanagan and M. Heidtman for their comments on this manuscript. This work was supported by a grant from the National Institute of General Medical Sciences.

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  1. Stefan Otte

    Present address: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA

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  1. Department of Biochemistry, Dartmouth Medical School, Hanover, 03755, NH, USA

    Stefan Otte & Charles Barlowe

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Correspondence to Charles Barlowe.

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Fig. S1, Fig. S2 and Table 1 (PDF 112 kb)

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Otte, S., Barlowe, C. Sorting signals can direct receptor-mediated export of soluble proteins into COPII vesicles. Nat Cell Biol 6, 1189–1194 (2004). https://doi.org/10.1038/ncb1195

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