Brudnick Neuropsychiatric Research Institute, Department of Neurobiology; Futai Lab; Graduate School of Biomedical Sciences
Amino Acids, Peptides, and Proteins | Neuroscience and Neurobiology
Synapse formation and regulation require interactions between pre- and postsynaptic proteins, notably cell adhesion molecules (CAMs). It has been proposed that the functions of neuroligins (Nlgns), postsynaptic CAMs, rely on the formation of trans-synaptic complexes with neurexins (Nrxns), presynaptic CAMs. Nlgn3 is a unique Nlgn isoform that localizes at both excitatory and inhibitory synapses. However, Nlgn3 function mediated via Nrxn interactions is unknown. Here, we demonstrate that Nlgn3 localizes at postsynaptic sites apposing vesicular glutamate transporter 3-expressing (VGT3+) inhibitory terminals and regulates VGT3+ inhibitory interneuron-mediated synaptic transmission in mouse organotypic slice cultures. Gene expression analysis of interneurons revealed that the αNrxn1+AS4 splice isoform is highly expressed in VGT3+ interneurons as compared with other interneurons. Most importantly, postsynaptic Nlgn3 requires presynaptic αNrxn1+AS4 expressed in VGT3+ interneurons to regulate inhibitory synaptic transmission. Our results indicate that specific Nlgn-Nrxn interactions generate distinct functional properties at synapses.
neuroscience, Neuroligin3, Neurexin1, hippocampus
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
bioRxiv 2020.05.27.119024; doi: https://doi.org/10.1101/2020.05.27.119024. Link to preprint on bioRxiv service.
Uchigashima M, Konno K, Demchak E, Cheung A, Watanabe T, Keener DG, Abe M, Le T, Sakimura K, Sasaoka T, Uemura T, Imamura Kawasawa Y, Watanabe M, Futai K. (2020). A Specific Neuroligin3-αNeurexin1 Code Regulates GABAergic Synaptic Function in Mouse Hippocampus. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2020.05.27.119024. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1708
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.