Monomeric type I and type III transforming growth factor-β receptors and their dimerization revealed by single-molecule imaging.
Transforming growth factor-β (TGF-β) binds with two transmembrane serine/threonine kinase receptors, type II (TβRII) and type I receptors (TβRI), and one accessory receptor, type III receptor (TβRIII), to transduce signals across cell membranes. Previous biochemical studies suggested that TβRI and TβRIII are preexisted homo-dimers. Using single-molecule microscopy to image green fluorescent protein-labeled membrane proteins, for the first time we have demonstrated that TβRI and TβRIII could exist as monomers at a low expression level. Upon TGF-β1 stimulation, TβRI follows the general ligand-induced receptor dimerization model for activation, but this process is TβRII-dependent. The monomeric status of the non-kinase receptor TβRIII is unchanged in the presence of TGF-β1. With the increase of receptor expression, both TβRI and TβRIII can be assembled into dimers on cell surfaces.
Zhang
Wei
W
Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Key Laboratory of Molecular Nanostructures and Nanotechnology, Chinese Academy of Sciences, Beijing 100190, China.
Yuan
Jinghe
J
Yang
Yong
Y
Xu
Li
L
Wang
Qiang
Q
Zuo
Wei
W
Fang
Xiaohong
X
Chen
Ye-Guang
YG
D045744:Cell Line, Tumor; D019281:Dimerization; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000378:metabolism*
D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I