MISTARGETING OF THE LECTIN ERGIC-53 TO THE ENDOPLASMIC-RETICULUM OF HELA-CELLS IMPAIRS THE SECRETION OF A LYSOSOMAL-ENZYME

ERGIC-53, a homo-oligomeric recycling protein associated with the ER-G olgi intermediate compartment (ERGIC), has properties of a mannose-sel ective lectin in vitro, suggesting that it may function as a transport receptor for glycoproteins in the early secretory pathway, To investi gate if ERGIC-53 is involved in glycoprotein secretion, a mutant form of this protein was generated that is incapable of leaving the ER, If expressed in HeLa cells in a tetracycline-inducible manner, this mutan t accumulated in the ER and retained the endogenous ERGIC-53 in this c ompartment, thus preventing its recycling, Mistargeting of ERGIC-53 to the ER did not alter the gross morphology of the early secretory path way, including the distribution of beta'-COP. However, it impaired the secretion of one major glycoprotein, identified as the precursor of t he lysosomal enzyme cathepsin C, while overexpression of wild-type ERG IC-53 had no effect on glycoprotein secretion. Transport of two other lysosomal enzymes and three post-Golgi membrane glycoproteins was unaf fected by inactivating the recycling of ERGIC-53. The results suggest that the recycling of ERGIC-53 is required for efficient intracellular transport of a small subset of glycoproteins, but it does not appear to be essential for the majority of glycoproteins.