Monomeric type I and type III transforming growth factor-β receptors and their dimerization revealed by single- molecule imaging

Transforming growth factor-beta (TGF-beta) binds with two transmembrane serine/threonine kinase receptors, type II (T beta RII) and type I receptors (T beta RI), and one accessory receptor, type III receptor (T beta RIII), to transduce signals across cell membranes. Previous biochemical studies suggested that T beta RI and T beta RIII are preexisted homo-dimers. Using single-molecule microscopy to image green fluorescent protein-labeled membrane proteins, for the first time we have demonstrated that T beta RI and T beta RIII could exist as monomers at a low expression level. Upon TGF-beta 1 stimulation, T beta RI follows the general ligand-induced receptor dimerization model for activation, but this process is T beta RII-dependent. The monomeric status of the non-kinase receptor T beta RIII is unchanged in the presence of TGF-beta 1. With the increase of receptor expression, both T beta RI and T beta RIII can be assembled into dimers on cell surfaces.