TY - JOUR
T1 - Transsynaptic Signaling by Activity-Dependent Cleavage of Neuroligin-1
AU - Peixoto, Rui T.
AU - Kunz, Portia A.
AU - Kwon, Hyungbae
AU - Mabb, Angela M.
AU - Sabatini, Bernardo L.
AU - Philpot, Benjamin D.
AU - Ehlers, Michael D.
N1 - Funding Information:
We thank Susana da Silva for technical assistance and data analysis. We thank Susana da Silva, Ian Davison, Cyril Hanus, Juliet Hernandez, Hyun-Soo Je, and Thomas Newpher for review of the manuscript. We thank Irina Lebedeva, Marguerita Klein, Sarah Lancaster, and Jaya Miriyala for excellent technical assistance. We thank Nils Brose for providing NLG1-KO mouse brains. Work in the laboratory of M.D.E. was supported by HHMI and grants from NIMH-NIH, NINDS-NIH, and the Simons Foundation. Work in the laboratory of B.D.P. is supported by grants from NEI-NIH and the Simons Foundation. R.T.P. was supported by the Portuguese FCT grant SFRH/BD/15217/2004. P.A.K. was supported by NICHD training Grant T32HD040127.
PY - 2012/10/18
Y1 - 2012/10/18
N2 - 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 Ca2+/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-1β (NRX1β). 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.
AB - 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 Ca2+/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-1β (NRX1β). 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.
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U2 - 10.1016/j.neuron.2012.07.006
DO - 10.1016/j.neuron.2012.07.006
M3 - Article
C2 - 23083741
AN - SCOPUS:84867712870
SN - 0896-6273
VL - 76
SP - 396
EP - 409
JO - Neuron
JF - Neuron
IS - 2
ER -