Brian Shonesy
Last active: 7/2/2015

Loss of Thr286 phosphorylation disrupts synaptic CaMKIIα targeting, NMDAR activity and behavior in pre-adolescent mice.

Gustin RM, Shonesy BC, Robinson SL, Rentz TJ, Baucum AJ, Jalan-Sakrikar N, Winder DG, Stanwood GD, Colbran RJ
Mol Cell Neurosci. 2011 47 (4): 286-92

PMID: 21627991 · PMCID: PMC3149813 · DOI:10.1016/j.mcn.2011.05.006

In order to provide insight into in vivo roles of CaMKIIα autophosphorylation at Thr286 during postnatal development, behavioral, biochemical, and electrophysiological phenotypes of pre-adolescent Thr286 to Ala CaMKIIα knock-in (T286A-KI) and WT mice were examined. T286A-KI mice displayed cognitive deficits in a novel object recognition test and an anxiolytic phenotype in the elevated plus maze, suggesting disruption of normal developmental processes. At the molecular level, the ratio of total CaMKIIα to CaMKIIβ in hippocampal lysates was significantly decreased≈2-fold in T286A-KI mice, and levels of both isoforms in synaptic subcellular fractions were decreased by≈80%. Total levels of GluA1 AMPA-glutamate receptor subunits and phosphorylation of GluA1 at the CaMKII site (Ser831) in synaptic fractions were unaltered, as were the frequency and amplitude of AMPAR-mediated spontaneous excitatory postsynaptic currents at hippocampal CA3-CA1 synapses. Synaptic levels of NMDA-glutamate receptor GluN1, GluN2A and GluN2B subunits also were unaltered. However, the reduced ratio of CaMKII to NMDAR subunits in synaptic fractions was linked to increased synaptic NMDAR-mediated currents in T286A-KI mice, apparently due to increased functional contributions by GluN2B NMDARs (assessed by Ro 25-6981 sensitivity). Thus, disruption of CaMKII synaptic targeting caused by elimination of Thr286 autophosphorylation leads to synaptic and behavioral deficits during pre-adolescence.

Copyright © 2011 Elsevier Inc. All rights reserved.

MeSH Terms (13)

Age Factors Animals Behavior, Animal Calcium-Calmodulin-Dependent Protein Kinase Type 2 Hippocampus Mice Mice, Inbred C57BL Patch-Clamp Techniques Phosphorylation Receptors, N-Methyl-D-Aspartate Synapses Synaptic Transmission Threonine

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