Molecular dissection of Neuroligin 2 and Slitrk3 reveals an essential framework for GABAergic synapse development

Li, J. et al. (2017) Molecular dissection of Neuroligin 2 and Slitrk3 reveals an essential framework for GABAergic synapse development. Neuron, 96(4), 808-826.e8. (doi: 10.1016/j.neuron.2017.10.003) (PMID:29107521) (PMCID:PMC5957482)

Abstract

In the brain, many types of interneurons make functionally diverse inhibitory synapses onto principal neurons. Although numerous molecules have been identified to function in inhibitory synapse development, it remains unknown whether there is a unifying mechanism for development of diverse inhibitory synapses. Here we report a general molecular mechanism underlying hippocampal inhibitory synapse development. In developing neurons, the establishment of GABAergic transmission depends on Neuroligin 2 (NL2), a synaptic cell adhesion molecule (CAM). During maturation, inhibitory synapse development requires both NL2 and Slitrk3 (ST3), another CAM. Importantly, NL2 and ST3 interact with nanomolar affinity through their extracellular domains to synergistically promote synapse development. Selective perturbation of the NL2-ST3 interaction impairs inhibitory synapse development with consequent disruptions in hippocampal network activity and increased seizure susceptibility. Our findings reveal how unique postsynaptic CAMs work in concert to control synaptogenesis and establish a general framework for GABAergic synapse development.

• Item Type: Articles
• Additional Information: This work was supported by the NIH/NINDS Intramural Research Program (to W.L.), the NIH/NICHD Intramural Research Program (to C.J.M.), the NIH/NIDCD Intramural Research Program (to Y.-X.W. and R.S.P.), and the NIH/NEI Intramural Research Program (to L.D.).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Craig, Dr Mick
• Authors: Li, J., Han, W., Pelkey, K. A., Duan, J., Mao, X., Wang, Y.-X., Craig, M. T., Dong, L., Petralia, R. S., McBain, C. J., and Lu, W.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Neuron
• Publisher: Elsevier (Cell Press)
• ISSN: 0896-6273
• ISSN (Online): 1097-4199
• Published Online: 26 October 2017
• Copyright Holders: Copyright © 2017 Elsevier Inc.
• First Published: First published in Neuron 96(4): 808-826.e8
• Publisher Policy: Reproduced in accordance with the publisher copyright policy