Frontotemporal dementia mutant Tau promotes aberrant Fyn nanoclustering in hippocampal dendritic spines.

ABSTRACT: The Src kinase Fyn plays critical roles in memory formation and Alzheimer's disease. Its targeting to neuronal dendrites is regulated by Tau via an unknown mechanism. As nanoclustering is essential for efficient signaling, we used single-molecule tracking to characterize the nanoscale distribution of Fyn in mouse hippocampal neurons, and manipulated the expression of Tau to test whether it controls Fyn nanoscale organization. We found that dendritic Fyn exhibits at least three distinct motion states, two of them associated with nanodomains. Fyn mobility decreases in dendrites during neuronal maturation, suggesting a dynamic synaptic reorganization. Removing Tau increases Fyn mobility in dendritic shafts, an effect that is rescued by re-expressing wildtype Tau. By contrast, expression of fr

SUBMITTER: Padmanabhan P 

PROVIDER: S-EPMC6592683 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature