- 作者：Kanzo Suzuki ; Fumitaka Kawakami ; Hisashi Sasaki ; Hiroko Maruyama ; Kenzo Ohtsuki
- 关键词：Tau protein ; Syndapin 1 ; Protein kinase C
; //www.sciencedirect.com/scidirimg/entities/25b.gif"" alt=""var epsilon"" title=""var epsilon"" border=""0""> ; Casein kinase 1 ; Glycogen synthase kinase-3β ; Sulfatide ; Cholesterol-3-sulfate ; Rat brain
- 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
- 出版年：2009
- 出版时间：March 2009
- 年：2009
- 卷：1790
- 期：3
- 页码：188-197
- 全文大小：1139 K
BackgroundWe recently reported that both sulfatide and cholesterol-3-sulfate (SCS) function as potent stimulators for the GSK-3β-mediated phosphorylation of tau protein (TP) in vitro [J. Biochem. 143 (2008) 359–367].Methods
By means of successive gel filtration on a Superdex 200 pg column and three distinct ion-exchange column chromatographies, TP and its associated proteins were highly purified from the extract of rat brain.
Results
We found that (i) syndapin 1 and novel protein kinase C (nPKC) were identified as the TP-associated proteins; (ii) SCS highly stimulated the phosphorylation of TP and syndapin 1 by nPKC as well as CK1; (iii) the full phosphorylation of TP and syndapin 1 by nPKC in the presence of sulfatide resulted in their dissociation; (iv) TP primed by CK1 functioned as an effective phosphate acceptor for GSK-3β; (v) syndapin 1 highly stimulated the GSK-3β-mediated phosphorylation of TP; and (vi) TP isoforms were highly expressed in aged brain, whereas syndapin 1 was consistently detected in adult brain, but not in newborn brain.
General significance
These results provided here suggest that (i) TP-associated nPKC suppresses the GSK-3β-mediated phosphorylation of TP through the phosphorylation of GSK-3β by the kinase in vitro; and (ii) SCS act as effective sole mediators to induce the GSK-3β-mediated high phosphorylation of both TP and its associated syndapin 1 involved in the biochemical processes of neuronal diseases, including Alzheimer's disease.