GSK3 alpha/beta (Glycogen Synthase Kinases alpha/beta) are serine/threonine kinases ubiquitously expressed in the nervous system. GSK3’s appear to be critical for LTD formation and overactivation of GSK3 inhibits LTP expression. Here we report that GSK3 regulate expression of Arc/Arg3.1 protein (Activity Regulated Cytoskeleton Associated Protein/Activity Regulated Gene 3.1), involved in diverse forms of synaptic plasticity, including LTP, LTD and homeostatic plasticity. We hypothesize that Arc could be one of the putative GSK3 effectors in neurons. The combination of low dose NMDA and GSK3 inhibitors upregulated Arc expression at the protein but not at the mRNA level. Recombinant Arc protein is phosphorylated in vitro by GSK3 beta. Currently, we are characterizing the mechanism of GSK3-dependent Arc degradation. We also observed that the co-treatment of neurons with GSK3 inhibitors and NMDA induced alterations in the dendritic spine morphology. We are employing shRNA technology to determine if Arc contributes to the observed alterations in dendritic spines morphology and what is the role of GSK3-dependent Arc degradation in different forms of synaptic plasticity. Supported by 7FP EU grant 223276 “NeuroGSK3” and NCN 05397 grant from National Center for Science.
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.