betaglycan

Betaglycan, also called transforming growth factor beta type III receptor (TGFBR3), is a cell surface proteoglycan that functions as a co-receptor for several members of the TGF-β family. It is expressed in many tissues and modulates signaling by presenting ligands to signaling receptors, thereby regulating cellular responses such as proliferation, differentiation, and migration.

Structure and forms: Betaglycan is a single-pass transmembrane proteoglycan. Its large extracellular domain bears glycosaminoglycan chains of heparan sulfate and sometimes dermatan sulfate. The cytoplasmic tail is relatively short. A soluble form of betaglycan can be produced by proteolytic shedding of the ectodomain by metalloproteases, such as those in the ADAM family.

Mechanism of action: Betaglycan binds TGF-β isoforms, particularly TGF-β1, TGF-β2, and TGF-β3, with high affinity, and is essential for efficient TGF-β2 signaling in many cell types by presenting the ligand to the type II receptor (TGFBR2) and the type I receptor (ALK5). It can modulate signaling of activins and other ligands in certain contexts. The balance between membrane-bound and soluble forms, as well as tissue-specific expression, determines net signaling outcomes.

Biological significance: TGF-β signaling regulates development, tissue homeostasis, and remodeling. Altered TGFBR3 expression or shedding has been associated with cancer progression and fibrosis; loss of membrane TβRIII can reduce signaling in some contexts, while soluble receptor forms can act as decoys, sequestering ligands.

Genetics and interactions: The receptor is encoded by the TGFBR3 gene. It interacts with TGF-β ligands and signaling receptors and can cross-talk with other pathways, reflecting its role as a modulator of growth factor signaling.