Abstract
Tau is a microtubule-associated protein, localizing mainly in the axon of mature neurons. Phenotypic analysis of Tau knockout mice has revealed an impairment of synaptic plasticity but without gross changes in brain morphology. Since we previously described the presence of tau mRNA in the somatodendritic compartment, including the postsynapse, and demonstrated that it could be locally translated in response to glutamate, it appears that the regulated translation of synaptic tau can have a direct impact on synaptic function. Using SH-SY5Y cells, we herein confirm that glutamate dose-dependently regulates the translation of tau protein without altering tau mRNA levels. This is supported by the finding that cycloheximide blocks glutamate-stimulated increases in tau protein levels. Our observation that neural excitation can directly upregulate tau mRNA translation helps explain the pathological accumulation of tau in the somatodendrite.
Highlights
Intracellular inclusions of hyperphosphorylated tau protein and extracellular deposits of amyloid β (Aβ) are prominent neuropathological features in the brains of Alzheimer disease patients (Selkoe, 2004)
We showed that tau is essential for the induction of long-term depression (LTD) (Kimura et al, 2014), a phenomenon that can be explained by its presence in the somatodendritic compartment: non-axonal tau is translated from tau mRNA that is transported to the post-synapse as a complex comprised of mRNA binding protein and MyosinIV (Kobayashi et al, 2017)
Cell bodies and neurites of neural SH-SY5Y cells differentiated with retinoic acid (RA) displayed tau immunoreactivity when stained with a pan-tau antibody (Figure 1A)
Summary
Intracellular inclusions of hyperphosphorylated tau protein (neurofibrillary tangles, NFTs) and extracellular deposits of amyloid β (Aβ) are prominent neuropathological features in the brains of Alzheimer disease patients (Selkoe, 2004). In the AD brain, tau is hyperphosphorylated and forms fibrils that appear as neuropil threads in dendrites and as NFTs in the somato-dendritic compartment and axons (Kowall and Kosik, 1987). Evidence showing that NFT formation is preceded by a pre-tangle stage where non-fibrillar and hyperphosphorylated tau accumulates in the soma and dendrites of neurons (Gotz et al, 1995; Uchihara et al, 2001; Braak and Del Tredici, 2013) indicates that tau hyperphosphorylation occurs in the somatodendrite before its fibrillation and the appearance of neurofibrilar lesions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
