Local Somatodendritic Translation and Hyperphosphorylation of Tau Protein Triggered by AMPA and NMDA Receptor Stimulation

EBioMedicine

Yoshiyuki Soeda¹  Shunsuke Kobayashi²  Toru Tanaka²  Akihiko Takashima³  Osborne F.X. Almeida⁴ 

[1] Clinical Research Center, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295 Fukushima, Japan;Department of Biochemistry, School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi, Chiba 274-8555, Japan;Laboratory for Alzheimer's Disease, Department of Life Science, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, 171-8588, Tokyo, Japan;Max Planck Institute of Psychiatry, Kraeplinstrasse 2-10, 80804 Munich, Germany;

关键词: Somatodendritic localization of tau;    Tau mRNA;    RNP particle;    Local translation;    AMPA and NMDA receptors;   

DOI  :  10.1016/j.ebiom.2017.05.012

来源: DOAJ

【 摘 要 】

Tau is a major component of the neurofibrillary tangles (NFT) that represent a pathological hallmark of Alzheimer's disease (AD). Although generally considered an axonal protein, Tau is found in the somato-dendritic compartment of degenerating neurons and this redistribution is thought to be a trigger of neurodegeneration in AD. Here, we show the presence of tau mRNA in a dendritic ribonucleoprotein (RNP) complex that includes Ca2+-calmodulin dependent protein kinase (CaMK)IIα mRNA and that is translated locally in response to glutamate stimulation. Further, we show that Tau mRNA is a component of mRNP granules that contain RNA-binding proteins, and that it interacts with Myosin Va, a postsynaptic motor protein; these findings suggest that tau mRNA is transported into dendritic spines. We also report that tau mRNA localized in the somato-dendritic component of primary hippocampal cells and that a sub-toxic concentration of glutamate enhances local translation and hyperphosphorylation of tau, effects that are blocked by the gluatamatergic antagonists MK801 and NBQX. These data thus demonstrate that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-d-aspartate (NMDA) stimulation redistributes tau to the somato-dendritic region of neurons where it may trigger neurodegeneration.

【 授权许可】

Unknown