Nov 19, 2019

GSK-3β regulates the synaptic expression of NMDA receptors via phosphorylation of phosphatidylinositol 4 kinase type IIα

BioRxiv : the Preprint Server for Biology
Mascia AmiciG L Collingridge

Abstract

Understanding the normal functions of GSK-3β in the central nervous system is of major interest because deregulation of this kinase is strongly implicated in a variety of serious brain conditions, such as Alzheimer disease, bipolar disorder and schizophrenia. GSK-3β plays a role in the induction of NMDA receptor-dependent long-term depression (LTD) and several substrates for GSK-3β have been identified in this form of synaptic plasticity, including KLC-2, PSD-95 and tau. Stabilization of NMDA receptors at synapses has also been shown to involve GSK-3β, but the substrates involved are currently unknown. Recent work has identified phosphatidylinositol 4 kinase type IIα (PI4KIIα) as a neuronal GSK-3β substrate that can potentially regulate the surface expression of AMPA receptors. In the present study, we investigated the synaptic role of PI4KIIα in organotypic rat hippocampal slices. We found that knockdown of PI4KIIα had no effect on synaptic AMPA receptors but substantially inhibited synaptic NMDA receptors. Furthermore, the ability of the selective GSK-3 inhibitor, CT99021, to inhibit synaptic NMDA receptors was occluded in shRNA-PI4KIIα transfected neurons. The effects of knocking down PI4KIIα knockdown were fully rescued by ...Continue Reading

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Mentioned in this Paper

Study
glycogen synthase kinase 3 beta
Gene Knockdown Techniques
KNS2 protein, human
Schizophrenia
Regulation of Biological Process
Presynaptic density protein 95
Neurons
Long Term Depression
Protein Deregulation

About this Paper

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