N-Linked Oligosaccharides Direct the Differential Assembly and Secretion of Inhibin α- and βA-Subunit Dimers

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

doi:10.1210/me.2007-0050

Cited by 42 publications

(31 citation statements)

References 24 publications

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“…3b), and 56 kDa for free β B subunit and 27 kDa for mature β B subunit (Fig. 3c) were identified in the ovarian lysates, which is generally in accordance with previous reports [20][21][22]. It is noteworthy that the inhibin α antibody was able to detect only the precursor and that it could not detect the mature subunit as it did in other species [20].…”

Section: Expression Level Of Inhibin/activin Subunits Proteins In Wilsupporting

confidence: 91%

Immunohistochemical Localization of Inhibin/Activin Subunits in the Wild Ground Squirrel (Citellus dauricus brandt) Ovary

Sheng

Weng

Zhang

et al. 2012

Journal of Reproduction and Development

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Abstract. The intraovarian function of gonadally produced inhibin and activin has been extensively studied in experimental models for decades, yet their presence and function have been rarely reported in wild rodents. With our seasonal breeding model, the wild ground squirrel, we aimed to investigate the possible roles of these peptides in the seasonal folliculogenesis. Immunohistochemical staining and Western blotting have been used to detect the cellular localization and expression patterns of inhibin/activin subunits (α, β A and β B ). In the breeding season ovary, all three subunits were present in granulosa cells, theca cells of antral follicles and interstitial cells, with the strongest immunostaining in granulosa cells. Following ovulation, the corpora lutea become a major site of inhibin/activin synthesis. In the nonbreeding season ovary, inhibin/activin α and β A subunits were weakly immunopositive in granulosa cells of early stage follicles, while β B subunit was undetectable. The expression level of inhibin/activin subunit proteins were generally higher in the ovaries of the breeding season, and then decreased to a relatively low level during the nonbreeding season. The dynamic expression of inhibin/activin subunits indicated that they might play important paracrine and/or autocrine roles during the seasonal folliculogenesis of the wild ground squirrel. Key words: Folliculogenesis, Immunohistochemistry, Inhibin/activin subunits, Ovary, Wild ground squirrel (J. Reprod. Dev. 58: [531][532][533][534][535][536] 2012) I nhibin and activin are prototypical members of the transforming growth factor β (TGFβ) superfamily of ligands and receptors, which are temporally and spatially widespread and functionally diverse [1][2][3]. Inhibin is composed of an α-subunit disulfide linked to a β subunit, and the particular isoform of inhibin is named for the β subunit present in that molecule (inhibin A, α/β A , and inhibin B, α/β B ). Activins are homodimers of the inhibin β subunits (activin A, β A /β A , activin B, β B /β B , and activin AB, β A /β B ) [4][5][6]. Biological roles for activin have been proposed in a number of reproductive organs including the gonads, pituitary, and uterus, where it regulates processes such as folliculogenesis, spermatogenesis, and pregnancy, while the primary role of inhibin appears to be antagonism of inhibin/ activin signaling in many cells, including pituitary gonadotrope FSH synthesis and ovarian theca and testicular Leydig cell androgen production [7][8][9]. In the ovary, inhibin and activin, mainly produced by granulosa cells, are thought to be involved in many intraovarian roles during folliculogenesis [10]. Activin and several other TGF-β superfamily ligands play key roles in germ cell survival, in primordial follicle assembly and in follicle growth from the preantral to midantral stages, and exert paracrine actions on theca cells to attenuate LH-dependent androgen production in small-to medium-sized antral follicles [11,12]. Changes in intrafollicular activins may contribu...

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Section: Expression Level Of Inhibin/activin Subunits Proteins In Wilsupporting

confidence: 91%

Immunohistochemical Localization of Inhibin/Activin Subunits in the Wild Ground Squirrel (Citellus dauricus brandt) Ovary

Sheng

Weng

Zhang

et al. 2012

Journal of Reproduction and Development

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“…1C) was also produced with the QuikChange method using primers spanning, but not including, the N-terminal region of the ␣-subunit. The template for this reaction was either a pcDNA5 bicistronic plasmid containing the human ␣-and ␤A-subunits separated by an internal ribosomal entry site (38) or a pcDNA5 plasmid containing the human ␣-subunit. The A257T ␣-subunit mutant was produced by PCR using the QuikChange procedure.…”

Section: Methodsmentioning

confidence: 99%

“…Three isogenic cell lines were generated for each ligand: wild type inhibin, ␣ HextϪ /␤A, ␣ A257T /␤A, human and chicken wild type free ␣-subunit (␣ Hwt or ␣ CHwt ), and human free ␣-subunit N-terminal deletion mutant (␣ HextϪ ) ( Fig. 1C) (38). At 80 -100% confluence, media was exchanged for DMEM-F12 or F12 serum-free media and cells were grown for 3-4 days before media collection.…”

Section: Methodsmentioning

confidence: 99%

Inhibin α-Subunit N Terminus Interacts with Activin Type IB Receptor to Disrupt Activin Signaling

Zhu

Lin

Zou

et al. 2012

Journal of Biological Chemistry

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Background:The inhibin ␤-subunit interacts with activin type II receptor to antagonize activin signaling. Results: The inhibin ␣-subunit N terminus binds ALK4 to antagonize activin signaling. Conclusion: Inhibin ␣-subunit binding to ALK4 supports potent antagonism of constitutive activin-stimulated FSH production in pituitary cells. Significance: Understanding the mechanisms underlying control of pituitary FSH synthesis may provide treatment approaches to reproductive endocrine disorders.

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“…Stl-B and Stl-C have two potential N-glycosylation targets (NxS/T) within Stl-B's putative prodomain, and three additional sites within the thrombospondin and cys-rich regions are shared by all three Stl isoforms. Since N-glycosylation can affect protein folding and secretion efficiency [e.g., synaptotagmin 1 and inhibin/activin (Han et al 2004;Antenos et al 2007)], it is possible that these sites in Stl either facilitate secretion in the absence of a strong signal peptide (Stl-B) or boost a weak signal sequence (Stl-A). Other ADAMTS oligosaccharide modifications, C-mannosylation and O-fucosylation, typically occur within the TSRs and can be important for function (e.g., ADAMTS13) (Gonzalez De Peredo et al 2002;Paakkonen et al 2006;Ricketts et al 2007).…”

Section: Discussionmentioning

confidence: 99%

stall Encodes an ADAMTS Metalloprotease and Interacts Genetically With Delta in Drosophila Ovarian Follicle Formation

2009

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Ovarian follicle formation in Drosophila melanogaster requires stall (stl) gene function, both within and outside the ovary, for follicle individualization, stalk cell intercalation, and oocyte localization. We have identified the stl transcript as CG3622 and confirmed the presence of three alternatively spliced isoforms, contrary to current genome annotation. Here we show that the gene is expressed in both ovarian and brain tissues, which is consistent with previous evidence of an ovary nonautonomous function. On the basis of amino acid sequence, stl encodes a metalloprotease similar to the ''a disintegrin and metalloprotease with thrombospondin'' (ADAMTS) family. Although stl mutant ovaries fail to maintain the branched structure of the fusome and periodically show improperly localized oocytes, stl mutants do not alter oocyte determination. Within the ovary, stl is expressed in pupal basal stalks and in adult somatic cells of the posterior germarium and the follicular poles. Genetically, stl exhibits a strong mutant interaction with Delta (Dl), and Dl mutant ovaries show altered stl expression patterns. Additionally, a previously described genetic interactor, daughterless, also modulates stl expression in the somatic ovary and may do so directly in its capacity as a basic helix-loop-helix (bHLH) transcription factor. We propose a complex model of long-range extraovarian signaling through secretion or extracellular domain shedding, together with local intraovarian protein modification, to explain the dual sites of Stl metalloprotease function in oogenesis.

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N-Linked Oligosaccharides Direct the Differential Assembly and Secretion of Inhibin α- and β_A-Subunit Dimers

Cited by 42 publications

References 24 publications

Immunohistochemical Localization of Inhibin/Activin Subunits in the Wild Ground Squirrel (<i>Citellus dauricus brandt</i>) Ovary

Immunohistochemical Localization of Inhibin/Activin Subunits in the Wild Ground Squirrel (<i>Citellus dauricus brandt</i>) Ovary

Inhibin α-Subunit N Terminus Interacts with Activin Type IB Receptor to Disrupt Activin Signaling

stall Encodes an ADAMTS Metalloprotease and Interacts Genetically With Delta in Drosophila Ovarian Follicle Formation

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