Mistargeting of the Lectin ERGIC-53 to the Endoplasmic Reticulum of HeLa Cells Impairs the Secretion of a Lysosomal Enzyme

• Published in: The Journal of cell biology Vol. 142; no. 2; pp. 377 - 389
• Main Authors: Vollenweider, Florence, Kappeler, Felix, Itin, Christian, Hauri, Hans-Peter
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 27.07.1998; The Rockefeller University Press
• Subjects: Amino Acid Sequence; Antibodies; Biological Transport, Active; Cathepsin C; Cells; Cellular biology; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - genetics; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - metabolism; Endoplasmic Reticulum, Rough - metabolism; Enzyme Precursors - genetics; Enzyme Precursors - metabolism; Enzymes; Gene Expression; Glycoproteins; Glycoproteins - metabolism; Golgi Apparatus - metabolism; HeLa Cells; Humans; Lectins; Lectins - genetics; Lectins - metabolism; Lysosomes - enzymology; Mannose-Binding Lectins; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular Sequence Data; Mutation; Proteins; Receptors; Recycling; Secretion; Secretory pathway; Transformation, Genetic
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.142.2.377

ERGIC-53, a homo-oligomeric recycling protein associated with the ER-Golgi intermediate compartment (ERGIC), has properties of a mannose-selective lectin in vitro, suggesting that it may function as a transport receptor for glycoproteins in the early secretory pathway. To investigate 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 mutant accumulated in the ER and retained the endogenous ERGIC-53 in this compartment, thus preventing its recycling. Mistargeting of ERGIC-53 to the ER did not alter the gross morphology of the early secretory pathway, including the distribution of β′-COP. However, it impaired the secretion of one major glycoprotein, identified as the precursor of the lysosomal enzyme cathepsin C, while overexpression of wild-type ERGIC-53 had no effect on glycoprotein secretion. Transport of two other lysosomal enzymes and three post-Golgi membrane glycoproteins was unaffected 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.