title: CaMKII phosphorylation of neuroligin-1 regulates excitatory synapses.
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.
authors: 1] Department of Biology, The Johns Hopkins University, Baltimore, Maryland, USA. [2] Receptor Biology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors: Michael A
authors: MA
authors: Bemben
authors: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA.
authors: Seth L
authors: SL
authors: Shipman
authors: Receptor Biology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors: Takaaki
authors: T
authors: Hirai
authors: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA.
authors: Bruce E
authors: BE
authors: Herring
authors: Protein/Peptide Sequencing Facility, NINDS, NIH, Bethesda, Maryland, USA.
authors: Yan
authors: Y
authors: Li
authors: Receptor Biology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors: John D
authors: JD
authors: Badger
authors: 1] Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA. [2] Department of Physiology, University of California, San Francisco, San Francisco, California, USA.
authors: Roger A
authors: RA
authors: Nicoll
authors: Synaptic Physiology Section, NINDS, NIH, Bethesda, Maryland, USA.
authors: Jeffrey S
authors: JS
authors: Diamond
authors: Receptor Biology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors: Katherine W
authors: KW
authors: Roche
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001596:Benzylamines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology*; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000235:genetics; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018091:Receptors, AMPA / Q000235:genetics; D012683:Sensory Deprivation / Q000502:physiology; D020539:Sequence Analysis, Protein; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*; D014162:Transfection; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D014793:Visual Cortex / Q000378:metabolism
chemical_list: D001596:Benzylamines; D001640:Bicuculline; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D015816:Cell Adhesion Molecules, Neuronal; D000076122:Disks Large Homolog 4 Protein; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D051528:Guanylate Kinases; D008164:Luminescent Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; D018091:Receptors, AMPA; D013449:Sulfonamides; D050598:Vesicular Glutamate Transport Protein 1; C501447:Dlg4 protein, mouse; C425780:KN 92; C093438:neuroligin 1