The study explores the behavioral effects and regulatory mechanisms of the small Rho-family GTPase Rac1 at presynaptic terminals in the hippocampus. Key findings:
Presynaptic Rac1 inhibition selectively impairs spatial working memory in mice, without affecting other types of memory like spatial reference memory and fear memory. In contrast, postsynaptic Rac1 inhibition impairs remote fear memory.
Electron microscopy analysis reveals that presynaptic Rac1 inhibition affects synaptic structures, including an increase in dendritic spine size and changes in synaptic vesicle morphology and distribution.
Proteomic mapping of presynaptic Rac1 interactions identifies key kinases like Mink1 and Group I PAKs that may phosphorylate synaptic proteins like Syntaxin-1b and Synaptotagmin-1. These phosphorylation events could regulate synaptic vesicle dynamics and contribute to the observed effects on spatial working memory.
The findings suggest a compartmentalized role of Rac1 in hippocampal-dependent cognitive processes, with presynaptic Rac1 selectively regulating spatial working memory through phosphoregulation of synaptic proteins and modulation of synaptic vesicle organization and dynamics.
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by Kim,J., Bust... klo www.biorxiv.org 03-19-2024
https://www.biorxiv.org/content/10.1101/2024.03.18.585488v1Syvällisempiä Kysymyksiä