ORCID ID

http://orcid.org/0000-0001-6483-1709

Document Type

Article

Publication Date

6-11-2018

Publication Title

eLife

Abstract

Trypsin-like serine proteases are essential in physiological processes. Studies have shown that N-glycans are important for serine protease expression and secretion, but the underlying mechanisms are poorly understood. Here, we report a common mechanism of N-glycosylation in the protease domains of corin, enteropeptidase and prothrombin in calnexin-mediated glycoprotein folding and extracellular expression. This mechanism, which is independent of calreticulin and operates in a domain-autonomous manner, involves two steps: direct calnexin binding to target proteins and subsequent calnexin binding to monoglucosylated N-glycans. Elimination of N-glycosylation sites in the protease domains of corin, enteropeptidase and prothrombin inhibits corin and enteropeptidase cell surface expression and prothrombin secretion in transfected HEK293 cells. Similarly, knocking down calnexin expression in cultured cardiomyocytes and hepatocytes reduced corin cell surface expression and prothrombin secretion, respectively. Our results suggest that this may be a general mechanism in the trypsin-like serine proteases with N-glycosylation sites in their protease domains.

Comments

This work was supported by grants from the NIH (HL126697), the National Science Foundation of China (91639116, 81671485) and Priority Academic Program Development of Jiangsu Higher Education Institutions. The Orbitrap Elite instrument used by the Proteomic Core at the Lerner Research Institute of the Cleveland Clinic was purchased via an NIH shared instrument grant (1S10RR031537-01).

DOI

10.7554/eLife.35672

Version

Publisher's PDF

Volume

7

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