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

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