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CaMKII phosphorylation of neuroligin-1 regulates excitatory synapses.

Nature neuroscience | Jan 26, 2014

http://www.ncbi.nlm.nih.gov/pubmed/24336150

Neuroligins are postsynaptic cell adhesion molecules that are important for synaptic function through their trans-synaptic interaction with neurexins (NRXNs). The localization and synaptic effects of neuroligin-1 (NL-1, also called NLGN1) are specific to excitatory synapses with the capacity to enhance excitatory synapses dependent on synaptic activity or Ca(2+)/calmodulin kinase II (CaMKII). Here we report that CaMKII robustly phosphorylates the intracellular domain of NL-1. We show that T739 is the dominant CaMKII site on NL-1 and is phosphorylated in response to synaptic activity in cultured rodent neurons and sensory experience in vivo. Furthermore, a phosphodeficient mutant (NL-1 T739A) reduces the basal and activity-driven surface expression of NL-1, leading to a reduction in neuroligin-mediated excitatory synaptic potentiation. To the best of our knowledge, our results are the first to demonstrate a direct functional interaction between CaMKII and NL-1, two primary components of excitatory synapses.

Pubmed ID: 24336150 RIS Download

Mesh terms: Animals | Animals, Newborn | Benzylamines | Bicuculline | Calcium-Calmodulin-Dependent Protein Kinase Type 2 | Cell Adhesion Molecules, Neuronal | Cells, Cultured | Dose-Response Relationship, Drug | Electric Stimulation | Excitatory Amino Acid Antagonists | Excitatory Postsynaptic Potentials | Female | GABA Antagonists | Gene Expression Regulation | Guanylate Kinase | Hippocampus | Humans | Immunoprecipitation | In Vitro Techniques | Luminescent Proteins | Male | Mass Spectrometry | Membrane Proteins | Mice | Mice, Inbred C57BL | MicroRNAs | Mutation | Neurons | Patch-Clamp Techniques | Phosphorylation | Protein Kinase Inhibitors | Receptors, AMPA | Sensory Deprivation | Sequence Analysis, Protein | Statistics, Nonparametric | Sulfonamides | Synapses | Transfection | Vesicular Glutamate Transport Protein 1 | Visual Cortex

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Associated grants

  • Agency: NIMH NIH HHS, Id: 5 R37 MH038256
  • Agency: NIMH NIH HHS, Id: R37 MH038256
  • Agency: Intramural NIH HHS, Id:

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