Components of RNA granules affect their localization and dynamics in neuronal dendrites.

In neurons, RNA transport is important for local protein synthesis. mRNAs are transported along dendrites as large RNA granules. The localization and dynamics of Puralpha and Staufen1 (Stau1), major components of RNA transport granules, were investigated in cultured hippocampal neurons. Puralpha-positive granules were localized in both the shafts and spines of dendrites. In contrast, Stau1-positive granules tended to be localized mainly in dendritic shafts. More than 90% of Puralpha-positive granules were positive for Stau1 in immature dendrites, while only half were positive in mature dendrites. Stau1-negative Puralpha granules tended to be stationary with fewer anterograde and retrograde movements than Stau1-positive Puralpha granules. After metabotropic glutamate receptor 5 activation, Stau1-positive granules remained in the dendritic shafts, while Puralpha granules translocated from the shaft to the spine. The translocation of Puralpha granules was dependent on myosin Va, an actin-based molecular motor protein. Collectively our findings suggest the possibility that the loss of Stau1 in Puralpha-positive RNA granules might promote their activity-dependent translocation into dendritic spines, which could underlie the regulation of protein synthesis in synapses.

Beta-amyloid prevents excitotoxicity via recruitment of glial glutamate transporters.

Amyloid beta-protein (Abeta), a putative pathogenic endotoxin involved in Alzheimer's disease, induces redistribution of glutamate transporters in astrocytes and promotes their pump activity. Because the transporters are assumed to protect neurons against excitotoxicity by removing extracellular glutamate, we hypothesized that Abeta alters the vulnerability of neurons to glutamate. Cerebrocortical neuron-astroglial co-cultures were exposed to glutamate, the concentration of which was selected so that only 20% of the neurons exhibited degeneration. When cultures were pre-treated with Abeta, exposure to the same "mild" glutamate concentration failed to damage neurons. The Abeta-induced protection was abolished by a glial glutamate transporter inhibitor. Thus, Abeta can alleviate excitotoxicity through glutamate transporter activity. The present results may challenge prevailing concepts that Abeta-induced neuron loss causes Alzheimer's dementia and also provide practical insights into neuro-glial interactions in glutamate toxicity.