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Appenzeller-Herzog, C ; Roche, AC ; Nufer, O ; Hauri, HP

pH-induced conversion of the transport lectin ERGIC-53 triggers glycoprotein release

Journal of Biological Chemistry 279 (13) 12943-12950

par Administrateur - publié le

Abstract :

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.