MT3-MMP Promotes Excitatory Synapse Formation by Promoting Nogo-66 Receptor Ectodomain Shedding

作者：Sanz Ricardo L.; Ferraro Gino B.; Kacervosky Johannes; Salesse Charleen; Gowing Elizabeth; Hua Luyang; Rambaldi Isabel; Beaubien Francois; Holmbeck Kenn; Cloutier J. F.; Levesque Martin; Murai Keith; Fournier Alyson E.^*

来源：Journal of Neuroscience, 2018, 38(3): 518-529.

DOI：10.1523/JNEUROSCI.0962-17.2017

• metalloproteinase
• Nogo receptor
• synaptogenesis

Cell-surface molecules are dynamically regulated at the synapse to assemble and disassemble adhesive contacts that are important for synaptogenesis and for tuning synaptic transmission. Metalloproteinases dynamically regulate cellular behaviors through the processing of cell surface molecules. In the present study, we evaluated the role of membrane-type metalloproteinases (MT-MMPs) in excitatory synaptogenesis. We find that MT3-MMP and MT5-MMP are broadly expressed in the mouse cerebral cortex and that MT3-MMP loss-of-function interferes with excitatory synapse development in dissociated cortical neurons and in vivo. We identify Nogo-66 receptor (NgR1) as anMT3-MMPsubstrate that is required for MT3-MMP-dependent synapse formation. Introduction of the shed ectodomain of NgR1 is sufficient to accelerate excitatory synapse formation in dissociated cortical neurons and in vivo. Together, our findings support a role for MT3-MMP-dependent shedding of NgR1 in regulating excitatory synapse development.

• 出版日期2018-1-17
• 单位McGill