Complex formation of a brain-derived neurotrophic factor and glycosaminoglycans.
Glycosaminoglycans (GAGs), large anionic glycopolymers, are the glycan portion of proteoglycans and are important components of the extracellular matrix. Recently we reported that polysialic acid, a polyanionic glycopolymer specific to the brain, binds neurotrophic factors to form a large complex. It is not clear whether GAGs also bind neurotrophic factors to form a large complex. In the present study, we demonstrate that a brain-derived neurotrophic factor (BDNF) dimer directly binds GAGs other than chondroitin and hyaluronic acid to form a large complex. Neurotrophin-3 showed similar GAG binding properties. Furthermore, BDNF, after forming a large complex with GAG, bound to the BDNF receptors tropomyosin-related kinase (Trk) B and p75 neurotrophin receptor (NTR). These findings suggest that GAGs function to produce a reservoir of BDNF and other neurotrophic factors, and may serve to regulate their local concentrations on the cell surface.
Kanato
Yukihiro
Y
Graduate School of Bioagricultural Sciences and the Bioscience and Biotechnology Center, Nagoya University, Japan.
Ono
Sayaka
S
Kitajima
Ken
K
Sato
Chihiro
C
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
D019208:Brain-Derived Neurotrophic Factor; D006025:Glycosaminoglycans