Role of the Lectin VIP36 in Post-ER Quality Control of Human α1-Antitrypsin

• Published in: Traffic (Copenhagen, Denmark) Vol. 11; no. 8; pp. 1044 - 1055
• Main Authors: Reiterer, Veronika, Nyfeler, Beat, Hauri, Hans-Peter
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.08.2010; Blackwell Publishing Ltd
• Subjects: BiP; endoplasmic reticulum; Golgi; kifunensine; L-type lectins; membrane traffic; recycling; yellow fluorescent protein fragment complementation
• DOI: 10.1111/j.1600-0854.2010.01078.x
• ISSN: 1398-9219

The leguminous-type (L-type) lectin VIP36 localizes to the Golgi apparatus and cycles early in the secretory pathway. In vitro, VIP36 binds high-mannose glycans with a pH optimum of 6.5, a value similar to the luminal pH of the Golgi apparatus. Although the sugar-binding properties of VIP36 in vitro have been characterized in detail, the function of VIP36 in the intact cell remains unclear as no convincing glycoprotein cargo has been identified. Here, we used yellow fluorescent protein (YFP) fragment complementation to identify luminal interaction partners of VIP36. By screening a human liver cDNA library, we identified the glycoprotein α1-antitrypsin (α1-AT) as a cargo of VIP36. The VIP36/α1-AT complex localized to Golgi and endoplasmic reticulum (ER). In the living cell, VIP36 bound exclusively to the high-mannose form of α1-AT. The binding was increased when complex glycosylation was prevented by kifunensine and abolished when the glycosylation sites of α1-AT were inactivated by mutagenesis. Silencing VIP36 accelerated α1-AT transport, arguing against a role of VIP36 in anterograde traffic. The complex formed by VIP36 and α1-AT in the Golgi recycled back to the ER. The combined data are most consistent with a function of VIP36 in post-ER quality control of α1-AT.