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Originally published In Press as doi:10.1074/jbc.M313245200 on January 12, 2004

J. Biol. Chem., Vol. 279, Issue 13, 12943-12950, March 26, 2004
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pH-induced Conversion of the Transport Lectin ERGIC-53 Triggers Glycoprotein Release*

Christian Appenzeller-Herzog{ddagger}, Annie-Claude Roche§, Oliver Nufer{ddagger}, and Hans-Peter Hauri{ddagger}||

From the {ddagger}Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland and §Glycobiologie, Centre de Biophysique Moleculaire, CNRS, F-45071 Orléans, France

The recycling mannose lectin ERGIC-53 operates as a transport receptor by mediating efficient endoplasmic reticulum (ER) export of some secretory glycoproteins. Binding of cargo to ERGIC-53 in the ER requires Ca2+. Cargo release occurs in the ERGIC, but the molecular mechanism is unknown. Here we report efficient binding of purified ERGIC-53 to immobilized mannose at pH 7.4, the pH of the ER, but not at slightly lower pH. pH sensitivity of the lectin was more prominent when Ca2+ concentrations were low. A conserved histidine in the center of the carbohydrate recognition domain was required for lectin activity suggesting it may serve as a molecular pH/Ca2+ sensor. Acidification of cells inhibited the association of ERGIC-53 with the known cargo cathepsin Z-related protein and dissociation of this glycoprotein in the ERGIC was impaired by organelle neutralization that did not impair the transport of a control protein. The results elucidate the molecular mechanism underlying reversible lectin/cargo interaction and establish the ERGIC as the earliest low pH site of the secretory pathway.


Received for publication, December 4, 2003 , and in revised form, January 8, 2004.

* This work was supported by the Swiss National Science Foundation and the University of Basel. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Research Director of Inserm.

|| To whom correspondence should be addressed. Tel.: 41-61-267-2222; Fax: 41-61-267-2208; E-mail: Hans-Peter.Hauri{at}unibas.ch.


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