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The lectin ERGIC-53 is a cargo transport receptor for glycoproteins

Nature Cell Biology volume 1, pages 330–334 (1999)Cite this article

Abstract

Soluble secretory proteins are transported from the endoplasmic reticulum (ER) to the ER–Golgi intermediate compartment (ERGIC) in vesicles coated with COP-II coat proteins. The sorting of secretory cargo into these vesicles is thought to involve transmembrane cargo-receptor proteins. Here we show that a cathepsin-Z-related glycoprotein binds to the recycling, mannose-specific membrane lectin ERGIC-53. Binding occurs in the ER, is carbohydrate- and calcium-ion-dependent and is affected by untrimmed glucose residues. Binding does not, however, require oligomerization of ERGIC-53, although oligomerization is required for exit of ERGIC-53 from the ER. Dissociation of ERGIC-53 occurs in the ERGIC and is delayed if ERGIC-53 is mislocalized to the ER. These results strongly indicate that ERGIC-53 may function as a receptor facilitating ER-to-ERGIC transport of soluble glycoprotein cargo.

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Figure 1: Crosslinking of ERGIC-53 to a 40K glycoprotein doublet identified as a cathepsin-Z-related protein (catZr).
Figure 2: Crosslinking of ERGIC-53 and catZr depends on a functional CRD of ERGIC-53 and on glycosylation of catZr.
Figure 3: CatZr binds to ERGIC-53 in the ER and dissociates in the ERGIC.
Figure 4: Role of calcium, glucose trimming and mannose trimming of catZr and oligomerization of ERGIC-53 on catZr–ERGIC-53 interaction, probed by crosslinking.

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Acknowledgements

We thank K. Bucher for technical assistance and M. Farquhar and W. Hong for providing antibodies to mannosidase II and Sec22b, respectively. H.A. was supported by a long-term EMBO fellowship. This work was supported by the Cantons of Basel and the Swiss National Science Foundation.

Correspondence and requests for materials should be addressed to H.-P.H.

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Author notes

  1. Helena Andersson

    Present address: Department of Bioscience, NOVUM, S-14157, Huddinge, Sweden

  2. Christian Appenzeller and Helena Andersson: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 70, Basel, CH-4056, Switzerland

    Christian Appenzeller, Helena Andersson, Felix Kappeler & Hans-Peter Hauri

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  1. Christian Appenzeller
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Correspondence to Hans-Peter Hauri.

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Appenzeller, C., Andersson, H., Kappeler, F. et al. The lectin ERGIC-53 is a cargo transport receptor for glycoproteins. Nat Cell Biol 1, 330–334 (1999). https://doi.org/10.1038/14020

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