Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Animals, Newborn
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Benzylamines / pharmacology
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Bicuculline / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
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Cell Adhesion Molecules, Neuronal / genetics
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Cell Adhesion Molecules, Neuronal / metabolism*
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Cells, Cultured
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Disks Large Homolog 4 Protein
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Dose-Response Relationship, Drug
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Electric Stimulation
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / genetics
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Excitatory Postsynaptic Potentials / physiology*
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Female
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GABA Antagonists / pharmacology
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Gene Expression Regulation / genetics
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Guanylate Kinases / metabolism
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Hippocampus / cytology
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Humans
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Immunoprecipitation
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In Vitro Techniques
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Luminescent Proteins / genetics
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Male
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Mass Spectrometry
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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MicroRNAs / pharmacology
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Mutation / genetics
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Neurons / drug effects
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Neurons / physiology*
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Patch-Clamp Techniques
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Phosphorylation / genetics
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Protein Kinase Inhibitors / pharmacology
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Receptors, AMPA / genetics
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Sensory Deprivation / physiology
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Sequence Analysis, Protein
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Statistics, Nonparametric
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Sulfonamides / pharmacology
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Synapses / physiology*
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Transfection
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Vesicular Glutamate Transport Protein 1 / metabolism
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Visual Cortex / metabolism
Substances
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Benzylamines
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Cell Adhesion Molecules, Neuronal
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Disks Large Homolog 4 Protein
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Dlg4 protein, mouse
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Excitatory Amino Acid Antagonists
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GABA Antagonists
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KN 92
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Luminescent Proteins
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Membrane Proteins
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MicroRNAs
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Protein Kinase Inhibitors
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Receptors, AMPA
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Sulfonamides
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Vesicular Glutamate Transport Protein 1
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neuroligin 1
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Guanylate Kinases
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glutamate receptor ionotropic, AMPA 1
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Bicuculline