期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 424, 期 1, 页码 82-88出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.06.071
关键词
Axon degeneration; Excitotoxicity; Microtubule stabilization; p150Glued
资金
- Osaka University Global COE Program (Frontier Biomedical Science Underlying Organelle Network Biology)
- Ministry of Education, Culture, Sports, Science & Technology, Japan
- JSPS
- Kurata Memorial Hitachi Science and Technology Foundation
- Takeda Science Foundation
- Japan Health Foundation
- Grants-in-Aid for Scientific Research [23650184] Funding Source: KAKEN
Glutamate excitotoxicity is implicated in chronic neurological disorders and acute CNS insults and causes neuronal degeneration including axons. The molecular mechanism underlying excitotoxicity-induced axon degeneration is poorly understood. Recently, we found that components of the dynein-dynactin complex that governs microtubule-dependent retrograde transport play important roles in modulating the process of excitotoxicity-induced neurodegeneration. Here we used hippocampal cultures and searched for pathways that function in concert with the components of the dynein-dynactin complex and identified microtubule stabilization as a cooperative pathway to suppress axon degeneration. We find that overexpression of p150Glued, a major component of the dynactin complex, and microtubule stabilization cooperatively suppress axon degeneration. The protective effect of p150Glued is dependent on the C-terminal region as excitotoxicity-induced C-terminal truncated form of p150Glued was unable to interact with APP cargo and altered the localization of APP in neurites when overexpressed. C-terminal truncation of p150Glued is not rescued by microtubule stabilization suggesting that the downstream effects of p150Glued and microtubule stabilization to protect axon degeneration are mutually exclusive. (C) 2012 Elsevier Inc. All rights reserved.
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