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

TY - JOUR

T1 - MT3-MMP Promotes Excitatory Synapse Formation by Promoting Nogo-66 Receptor Ectodomain Shedding

AU - Sanz, Ricardo L

AU - Ferraro, Gino B

AU - Kacervosky, Johannes

AU - Salesse, Charleen

AU - Gowing, Elizabeth

AU - Hua, Luyang

AU - Rambaldi, Isabel

AU - Beaubien, Francois

AU - Holmbeck, Kenn

AU - Cloutier, J F

AU - Lévesque, Martin

AU - Murai, Keith

AU - Fournier, Alyson E

N1 - Copyright © 2018 the authors 0270-6474/18/380518-12$15.00/0.

PY - 2018/1/17

Y1 - 2018/1/17

N2 - 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 indissociated cortical neurons and in vivo. WeidentifyNogo-66receptor (NgR1) as an MT3-MMP substrate 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.

AB - 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 indissociated cortical neurons and in vivo. WeidentifyNogo-66receptor (NgR1) as an MT3-MMP substrate 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.

U2 - 10.1523/jneurosci.0962-17.2017

DO - 10.1523/jneurosci.0962-17.2017

M3 - Journal article

C2 - 29196321

SN - 0270-6474

VL - 38

SP - 518

EP - 529

JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

IS - 3

ER -