Multivalent Tau/PSD-95 interactions arrest in vitro condensates and clusters mimicking the postsynaptic density.

ABSTRACT: Alzheimer's disease begins with mild memory loss and slowly destroys memory and thinking. Cognitive impairment in Alzheimer's disease has been associated with the localization of the microtubule-associated protein Tau at the postsynapse. However, the correlation between Tau at the postsynapse and synaptic dysfunction remains unclear. Here, we show that Tau arrests liquid-like droplets formed by the four postsynaptic density proteins PSD-95, GKAP, Shank, Homer in solution, as well as NMDA (N-methyl-D-aspartate)-receptor-associated protein clusters on synthetic membranes. Tau-mediated condensate/cluster arrest critically depends on the binding of multiple interaction motifs of Tau to a canonical GMP-binding pocket in the guanylate kinase domain of PSD-95. We further reveal that competitive b

SUBMITTER: Shen Z 

PROVIDER: S-EPMC10611757 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature