Specific Neuroligin3-alphaNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus
Uchigashima, Motokazu ; Konno, Kohtarou ; Demchak, Emily ; Cheung, Amy ; Watanabe, Takuya ; Keener, David G. ; Abe, Manabu ; Le, Timmy ; Sakimura, Kenji ; Sasaoka, Toshikuni ... show 4 more
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David G. Keener
Timmy Le
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Abstract
Synapse formation and regulation require signaling 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 alphaNrxn1+AS4 splice isoform is highly expressed in VGT3+ interneurons as compared with other interneurons. Most importantly, postsynaptic Nlgn3 requires presynaptic alphaNrxn1+AS4 expressed in VGT3+ interneurons to regulate inhibitory synaptic transmission. Our results indicate that specific Nlgn-Nrxn signaling generates distinct functional properties at synapses.
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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. Specific Neuroligin3-αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus. Elife. 2020 Dec 23;9:e59545. doi: 10.7554/eLife.59545. PMID: 33355091; PMCID: PMC7758064. Link to article on publisher's site