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 language | English |
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Pages (from-to) | 1670-1684 |
Number of pages | 15 |
Journal | Molecular Endocrinology |
Volume | 21 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2007 |