N-linked oligosaccharides direct the differential assembly and secretion of inhibin α- and βA-subunit dimers

Monica Antenos, Michelle Stemler, Irving Boime, Teresa K. Woodruff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The biosynthetic pathway governing inhibin heterodimer (α/β) and activin homodimer (β/β) assembly and secretion from ovarian granulosa cells is not fully understood. Here, we examined the role of inhibin subunit glycosylation in the assembly and secretion of mature inhibin A and activin A. Inhibition of subunit glycosylation by tunicamycin treatment of α-and βA-expressing CHO cell lines reduced inhibin but not activin secretion. Dimeric inhibin A is preferentially secreted from parental isogenic wild-type (wt) cell lines (αwtβwt). Mutation of a single glycosylation site at asparagine 268 (α Δ268βwt) reduces inhibin secretion by 78% and permits β/β assembly and secretion. Conversely, gain of a glycosylation (GOG) site in the analogous region of the βA- subunit (αwtβGOG327) enhances inhibin A secretion. The present study demonstrates that N-linked glycan sites direct heterodimer vs. homodimer assembly, and prevention of glycosylation abrogates inhibin secretion. These data support a definitive role for sitespecific N-glycosylation in governing inhibin/activin dimer assembly and secretion.

Original languageEnglish (US)
Pages (from-to)1670-1684
Number of pages15
JournalMolecular Endocrinology
Volume21
Issue number7
DOIs
StatePublished - Jul 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Fingerprint Dive into the research topics of 'N-linked oligosaccharides direct the differential assembly and secretion of inhibin α- and β<sub>A</sub>-subunit dimers'. Together they form a unique fingerprint.

Cite this