CaMKII phosphorylation of neuroligin-1 regulates excitatory synapses

This study shows that neuroligin-1, a trans-synaptic cell adhesion molecule for excitatory synapses, is directly phosphorylated by Ca 2+ /CaM kinase II in a neuronal activity–dependent manner in vitro and in vivo . The authors also show that this post-translational modification of neuroligin-1 regulates excitatory synaptic potentiation. 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.