The transforming growth factor-beta (TGF-ß) superfamily ligands regulate growth, differentiation, adhesion and apoptosis in various cell types and play a major role in testis development and spermatogenesis. Betaglycan (type III TGF-ß receptor) is an important coreceptor and modulator of TGF-ß superfamily ligands that acts through binding of distinct BMPs, inhibin, and TGF-ß1-3. It is highly expressed in testis and has a considerable impact on Leydig cell and seminiferous cord development. The regulation of TGF-ßs signalling by betaglycan is both positive and negative. Although the membrane-bound form of betaglycan increases binding of TGF-ßs to their receptors, the soluble form reduces actions of TGF-ßs. BMPs, inhibin and TGF-ß2 share betaglycan as a co-receptor and TGF-ß2 isoform is particularly dependent on betaglycan for signalling. However, little is known about interactions between these factors under physiological conditions. The betaglycan GAG chains can also influence TGF-ßs, activin A and BMPs ability to bind to their receptors. TGF-ßs, activins and BMPs are expressed significantly during testis development and thus might be involved in regulating functions of somatic and germ cells. The aim of this study was to investigate the effects of TGF-ß family signalling and possible cross-talks with other TGF-ß family pathways and their outcomes. Our study aims to elucidate the role of betaglycan conversion into its cleaved soluble form for TGF-ß superfamily signalling in a key testis target cell type, the Sertoli cell.
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