Tau target identification reveals NSF-dependent effects on AMPA receptor trafficking and memory formation.

ABSTRACT: Microtubule-associated protein tau is a central factor in Alzheimer's disease and other tauopathies. However, the physiological functions of tau are unclear. Here, we used proximity-labelling proteomics to chart tau interactomes in primary neurons and mouse brains in vivo. Tau interactors map onto pathways of cytoskeletal, synaptic vesicle and postsynaptic receptor regulation and show significant enrichment for Parkinson's, Alzheimer's and prion disease. We find that tau interacts with and dose-dependently reduces the activity of N-ethylmaleimide sensitive fusion protein (NSF), a vesicular ATPase essential for AMPA-type glutamate receptor (AMPAR) trafficking. Tau-deficient (tau^-/- ) neurons showed mislocalised expression of NSF and enhanced synaptic AMPAR surface levels, reversi

SUBMITTER: Prikas E 

PROVIDER: S-EPMC9475529 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature