ausblenden:
Schlagwörter:
AMYLOID-BETA OLIGOMERS; HIPPOCAMPAL-NEURONS; SYNAPTIC PLASTICITY;
NEUROFIBRILLARY TANGLES; MEMORY CONSOLIDATION; ALZHEIMERS-DISEASE;
MESSENGER-RNA; HEAD-INJURY; LOCALIZATION; TRANSPORTGeneral & Internal Medicine; Research & Experimental Medicine; Somatodendritic localization of tau; Tau mRNA; RNP particle; Local
translation; AMPA and NMDA receptors;
Zusammenfassung:
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)II alpha mRNA and that is translated locally in response to glutamate stimulation. Further, we show that TaumRNA 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. (C) 2017 The Authors. Published by Elsevier B.V.
