Peixoto_2012_Neuron_76_396

Adhesive contact between pre and postsynaptic neurons initiates synapse formation during brain development and provides a natural means of transsynaptic signaling Numerous adhesion molecules and their role during synapse development have been described in detail However once established the mechanisms of adhesive disassembly and its function in regulating synaptic transmission have been unclear Here we report that synaptic activity induces acute proteolytic cleavage of neuroligin-1 NLG1 a postsynaptic adhesion molecule at glutamatergic synapses NLG1 cleavage is triggered by NMDA receptor activation requires Ca(2+)/calmodulin-dependent protein kinase and is mediated by proteolytic activity of matrix metalloprotease 9 MMP9 Cleavage of NLG1 occurs at single activated spines is regulated by neural activity in vivo and causes rapid destabilization of its presynaptic partner neurexin-1beta NRX1beta In turn NLG1 cleavage depresses synaptic transmission by abruptly reducing presynaptic release probability Thus local proteolytic control of synaptic adhesion tunes synaptic transmission during brain development and plasticity.