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Nat Neurosci. 2014 Jan;17(1):56-64. doi: 10.1038/nn.3601. Epub 2013 Dec 15.

CaMKII phosphorylation of neuroligin-1 regulates excitatory synapses.

Author information

1
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.
2
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA.
3
Receptor Biology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, USA.
4
Protein/Peptide Sequencing Facility, NINDS, NIH, Bethesda, Maryland, USA.
5
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.
6
Synaptic Physiology Section, NINDS, NIH, Bethesda, Maryland, USA.

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.

PMID:
24336150
PMCID:
PMC3943352
DOI:
10.1038/nn.3601
[Indexed for MEDLINE]
Free PMC Article

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