Targeting of protein ERGIC-53 to the ER/ERGIC/cis-Golgi recycling pathway

A different explanation for the involvement of the lumenal domain in the targeting of ERGIC-53 could be a lumenal interaction with other proteins as a consequence of ERGIC-53's function. The finding of Arar et al. (1995) that ERGIC-53 is identical to an intracellular mannosespecific lectin points to the possibility that ERGIC-53 may facilitate ER to Golgi transport of newly synthesized gly-coproteins. Alternatively, ERGIC-53 may act as a chaperone downstream of calnexin Helenius, 1994) adding an additional level of quality control in the maturation process of glycoproteins. Either of these functions would involve the lumenal domain. Ligand binding may exert an allosteric effect on the cytoplasmic domain modulating the interaction with coatomer and thereby regulate the cycling of ERGIC-53. If so, a contribution of the lectin domain to sorting would only be apparent at moderate expression levels when enough ligand is available. The strong ER staining of highly overexpressed ERGIC-53 and GM as compared to the concentrated pattern seen under moderate expression would be consistent with this notion.