A Novel Role for hGas7b in Microtubular Maintenance POSSIBLE IMPLICATION IN TAU-ASSOCIATED PATHOLOGY IN ALZHEIMER DISEASE

被引:25
作者
Akiyama, Hirotada [1 ]
Gotoh, Aina [1 ]
Shin, Ryong-Woon [2 ]
Koga, Tomoe [1 ]
Ohashi, Tsubasa [1 ]
Sakamoto, Wataru [1 ]
Harada, Akihiro [4 ]
Arai, Hiroyuki [3 ]
Sawa, Akira [6 ,7 ]
Uchida, Chiyoko [5 ]
Uchida, Takafumi [1 ]
机构
[1] Tohoku Univ, Grad Sch Agr Sci, Dept Mol Enzymol, Sendai, Miyagi 9818555, Japan
[2] Tohoku Univ, Grad Sch Med, Dept Neuropathol, Sendai, Miyagi 9818555, Japan
[3] Tohoku Univ, Inst Dev Aging & Canc, Sendai, Miyagi 9818555, Japan
[4] Gunma Univ, Inst Mol & Cellular Regulat, Gunma 3718511, Japan
[5] Ibaraki Univ, Univ Hlth Ctr, Mito, Ibaraki 3108512, Japan
[6] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21287 USA
[7] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA
关键词
PC12; CELLS; PROTEIN; GAS7;
D O I
10.1074/jbc.M109.035998
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Here, we report a novel role for hGas7b (human growth arrest specific protein 7b) in the regulation of microtubules. Using a bioinformatic approach, we studied the actin-binding protein hGas7b with a structural similarity to the WW domain of a peptidyl prolyl cis/trans isomerase, Pin1, that facilitates microtubule assembly. Thus, we have demonstrated that hGas7b binds Tau at the WW motif and that the hGas7b/Tau protein complex interacts with the microtubules, promoting tubulin polymerization. Tau, in turn, contributes to protein stability of hGas7b. Furthermore, we observed decreased levels of hGas7b in the brains from patients with Alzheimer disease. These results suggest an important role for hGas7b in microtubular maintenance and possible implication in Alzheimer disease.
引用
收藏
页码:32695 / 32699
页数:5
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