Regulation of Mac-2BP secretion is mediated by its N-glycan binding to ERGIC-53.
The leguminous-type (L-type) lectin ER-Golgi intermediate compartment (ERGIC)-53, a homo-oligomeric endoplasmic reticulum (ER)-Golgi recycling protein, functions as a transport receptor for newly synthesized glycoproteins in the early secretory pathway. Although a limited subset of cargo glycoproteins transported by ERGIC-53, such as the coagulation factors V and VIII, cathepsin C and Z and α1-antitrypsin, has been identified, the exact role of the N-glycan binding of ERGIC-53 in the transport of secretory glycoproteins for ER exit has yet to be clarified. By screening a cDNA library isolated from HepG2 cells via a green fluorescent protein fragment complementation assay, we assessed several candidate luminal ERGIC-53-interacting partners and identified Mac-2 binding protein (Mac-2BP) as a novel ERGIC-53-transported cargo glycoprotein. Using an N-glycan-binding-deficient mutant of ERGIC-53 (N156A) or treatment with N-glycosylation processing inhibitors, as well as the introduction of the ER-mis-targeting mutant (KKAA), we demonstrated that the high-mannose-type N-glycan binding of ERGIC-53 contributes to its interaction with Mac-2BP, which is essential for the ERGIC-53-mediated ER-Golgi transport of nascent proteins during early secretion. Furthermore, we also provide evidence that MCFD2 is involved in the secretion of Mac-2BP. These observations reveal a distinct role for the N-glycan binding of ERGIC-53 in the receptor-mediated ER exit of newly synthesized Mac-2BP in the early secretion pathway.
['Chen|Yang|Y|', 'Hojo|Sanae|S|', 'Matsumoto|Naoki|N|', 'Yamamoto|Kazuo|K|']
D000951:Antigens, Neoplasm D005936:Glucans D057809:HEK293 Cells D006367:HeLa Cells D056945:Hep G2 Cells D006801:Humans D037241:Mannose-Binding Lectins D008562:Membrane Glycoproteins D008565:Membrane Proteins D009154:Mutation D011485:Protein Binding D021381:Protein Transport D055571:Secretory Pathway D033921:Vesicular Transport Proteins
Mac-2BP secretion ERGIC-53 cargo receptor