CaMKII triggers the diffusional trapping of surface AMPARs through phosphorylation of stargazin.

TitleCaMKII triggers the diffusional trapping of surface AMPARs through phosphorylation of stargazin.
Publication TypeJournal Article
Year of Publication2010
AuthorsOpazo P, Labrecque S, Tigaret CM, Frouin A, Wiseman PW, De Koninck P, Choquet D
JournalNeuron
Volume67
Issue2
Pagination239-52
Date Published2010 Jul 29
ISSN1097-4199
KeywordsAction Potentials, Animals, Animals, Newborn, Benzothiadiazines, Benzylamines, Calcium, Calcium Channels, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Cells, Cultured, Diffusion, Electric Stimulation, Embryo, Mammalian, Enzyme Activation, Excitatory Postsynaptic Potentials, Green Fluorescent Proteins, Hippocampus, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Models, Biological, Neurons, Phosphorylation, Protein Kinase Inhibitors, Protein Transport, Rats, Rats, Sprague-Dawley, Receptors, AMPA, Statistics, Nonparametric, Sulfonamides, Transfection
Abstract

The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is critically required for the synaptic recruitment of AMPA-type glutamate receptors (AMPARs) during both development and plasticity. However, the underlying mechanism is unknown. Using single-particle tracking of AMPARs, we show that CaMKII activation and postsynaptic translocation induce the synaptic trapping of AMPARs diffusing in the membrane. AMPAR immobilization requires both phosphorylation of the auxiliary subunit Stargazin and its binding to PDZ domain scaffolds. It does not depend on the PDZ binding domain of GluA1 AMPAR subunit nor its phosphorylation at Ser831. Finally, CaMKII-dependent AMPAR immobilization regulates short-term plasticity. Thus, NMDA-dependent Ca(2+) influx in the post-synapse triggers a CaMKII- and Stargazin-dependent decrease in AMPAR diffusional exchange at synapses that controls synaptic function.

DOI10.1016/j.neuron.2010.06.007
Alternate JournalNeuron
PubMed ID20670832
Grant List / / Canadian Institutes of Health Research / Canada

Funding

Our research endeavors are made possible by the following agencies:

Canadian Institutes of Health Research - Instituts de recherche en santé du Canada Fonds de recherche du Québec – Nature et technologies (FRQNT)Fonds de la recherche en santé du Québec NARSAD Natural Sciences and Engineering Research Council of Canada (NSERC) - Conseil de recherche en sciences naturelles et en génie du Canada (CRSNG)innovation.caHuman Frontier Science Program