Regulation of the Transforming Growth Factor-β Superfamily by Betaglycan

The type III transforming growth factor-β (TGF-β) receptor (TβRIII), also known as betaglycan (BG), is a membrane proteoglycan coreceptor that modulates the action of diverse members of the TGF-β superfamily of growth factors. Membrane bound BG is the precursor of a soluble receptor form generated by the proteolytic cleavage (shedding) of its extracellular region. While membrane BG enhances TGF-β binding to the type II TGF-β receptor, thereby increasing the activity of the factor (1), the soluble form sequesters the ligand, acting as a neutralizing agent of TGF-β (2). Recombinant soluble BG (rSBG) has been used successfully for treatment of diverse experimental pathologies in which TGF-β plays a physiopathological role. Given the recent discovery that BG shedding can be regulated, TGF-β modulatory properties of BG make it an attractive target for pathologies in which TGF-β action. Despite its reputation as an “accessory” TGF-β receptor, the mice lacking BG (BG-null or TβRIII−/−) exhibited an embryonic lethal phenotype (3), indicating that this coreceptor has essential, not yet identified, cellular functions. Here, we review the current knowledge of BG and discuss future scenarios for BG research and applications.