N-Linked Glycosylation-Dependent and -Independent Mechanisms Regulating CTRP12 Cleavage, Secretion, and Stability.

ABSTRACT: C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism. It circulates in plasma as a full-length protein or as a cleaved isoform generated by furin/PCSK3 cleavage. These isoforms preferentially activate different signaling pathways, and their ratio in plasma is altered in obesity and diabetes. Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability. Mass spectrometry analysis provided direct evidence of Asn-39 glycosylation. When N-linked glycosylation was inhibited by tunicamycin or abolished by the N39Q, N39A, or T41A mutation, CTRP12 cleavage was enhanced. Complex-type N-glycans on CTRP12 blocked cleavage by the Golgi-localized furin. In N-acety

SUBMITTER: Stewart AN 

PROVIDER: S-EPMC7694695 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature