Specific Neuroligin3–αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus
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),...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-12-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/59545 |
| _version_ | 1811199679585583104 |
|---|---|
| author | Motokazu Uchigashima Kohtarou Konno Emily Demchak Amy Cheung Takuya Watanabe David G Keener Manabu Abe Timmy Le Kenji Sakimura Toshikuni Sasaoka Takeshi Uemura Yuka Imamura Kawasawa Masahiko Watanabe Kensuke Futai |
| author_facet | Motokazu Uchigashima Kohtarou Konno Emily Demchak Amy Cheung Takuya Watanabe David G Keener Manabu Abe Timmy Le Kenji Sakimura Toshikuni Sasaoka Takeshi Uemura Yuka Imamura Kawasawa Masahiko Watanabe Kensuke Futai |
| author_sort | Motokazu Uchigashima |
| collection | DOAJ |
| description | 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 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 signaling generates distinct functional properties at synapses. |
| first_indexed | 2024-04-12T01:52:47Z |
| format | Article |
| id | doaj.art-8267cca0c2ad4e819a3495d720c4cf1d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:52:47Z |
| publishDate | 2020-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-8267cca0c2ad4e819a3495d720c4cf1d2022-12-22T03:52:54ZengeLife Sciences Publications LtdeLife2050-084X2020-12-01910.7554/eLife.59545Specific Neuroligin3–αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampusMotokazu Uchigashima0https://orcid.org/0000-0002-0878-2233Kohtarou Konno1Emily Demchak2Amy Cheung3https://orcid.org/0000-0002-4708-0293Takuya Watanabe4David G Keener5Manabu Abe6Timmy Le7Kenji Sakimura8Toshikuni Sasaoka9Takeshi Uemura10Yuka Imamura Kawasawa11Masahiko Watanabe12https://orcid.org/0000-0001-5037-7138Kensuke Futai13https://orcid.org/0000-0002-3433-3407Brudnick Neuropsychiatric Research Institute, Department of Neurobiology, University of Massachusetts Medical School, Worcester, United States; Department of Cellular Neuropathology, Brain Research Institute, Niigata University, Niigata, JapanDepartment of Anatomy, Faculty of Medicine, Hokkaido University, Sapporo, JapanDepartment of Biochemistry and Molecular Biology and Institute for Personalized Medicine, Pennsylvania State University College of Medicine, Hershey, United StatesBrudnick Neuropsychiatric Research Institute, Department of Neurobiology, University of Massachusetts Medical School, Worcester, United StatesBrudnick Neuropsychiatric Research Institute, Department of Neurobiology, University of Massachusetts Medical School, Worcester, United StatesBrudnick Neuropsychiatric Research Institute, Department of Neurobiology, University of Massachusetts Medical School, Worcester, United StatesDepartment of Animal Model Development, Brain Research Institute, Niigata University, Niigata, JapanBrudnick Neuropsychiatric Research Institute, Department of Neurobiology, University of Massachusetts Medical School, Worcester, United StatesDepartment of Animal Model Development, Brain Research Institute, Niigata University, Niigata, JapanDepartment of Comparative and Experimental Medicine, Brain Research Institute, Niigata University, Niigata, JapanDivision of Gene Research, Research Center for Supports to Advanced Science, Shinshu University, Nagano, Japan; Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Nagano, JapanDepartment of Biochemistry and Molecular Biology and Institute for Personalized Medicine, Pennsylvania State University College of Medicine, Hershey, United States; Department of Pharmacology Pennsylvania State University College of Medicine, Hershey, United StatesDepartment of Anatomy, Faculty of Medicine, Hokkaido University, Sapporo, JapanBrudnick Neuropsychiatric Research Institute, Department of Neurobiology, University of Massachusetts Medical School, Worcester, United StatesSynapse 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 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 signaling generates distinct functional properties at synapses.https://elifesciences.org/articles/59545trans-synaptic adhesionelectrophysiologyhippocampusinhibitory interneuron |
| spellingShingle | Motokazu Uchigashima Kohtarou Konno Emily Demchak Amy Cheung Takuya Watanabe David G Keener Manabu Abe Timmy Le Kenji Sakimura Toshikuni Sasaoka Takeshi Uemura Yuka Imamura Kawasawa Masahiko Watanabe Kensuke Futai Specific Neuroligin3–αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus eLife trans-synaptic adhesion electrophysiology hippocampus inhibitory interneuron |
| title | Specific Neuroligin3–αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus |
| title_full | Specific Neuroligin3–αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus |
| title_fullStr | Specific Neuroligin3–αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus |
| title_full_unstemmed | Specific Neuroligin3–αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus |
| title_short | Specific Neuroligin3–αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus |
| title_sort | specific neuroligin3 αneurexin1 signaling regulates gabaergic synaptic function in mouse hippocampus |
| topic | trans-synaptic adhesion electrophysiology hippocampus inhibitory interneuron |
| url | https://elifesciences.org/articles/59545 |
| work_keys_str_mv | AT motokazuuchigashima specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT kohtaroukonno specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT emilydemchak specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT amycheung specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT takuyawatanabe specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT davidgkeener specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT manabuabe specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT timmyle specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT kenjisakimura specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT toshikunisasaoka specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT takeshiuemura specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT yukaimamurakawasawa specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT masahikowatanabe specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus AT kensukefutai specificneuroligin3aneurexin1signalingregulatesgabaergicsynapticfunctioninmousehippocampus |