Transsynaptic modulation of kainate receptor functions by C1q-like proteins
Open accessAbstract
Postsynaptic kainate-type glutamate receptors (KARs) regulate synaptic network activity through their slow channel kinetics, most prominently at mossy fiber (MF)-CA3 synapses in the hippocampus. Nevertheless, how KARs cluster and function at these synapses has been unclear. Here, we show that C1q-like proteins C1ql2 and C1ql3, produced by MFs, serve as extracellular organizers to recruit functional postsynaptic KAR complexes to the CA3 pyramidal neurons. C1ql2 and C1ql3 specifically bound the amino-terminal domains of postsynaptic GluK2 and GluK4 KAR subunits and the presynaptic neurexin 3 containing a specific sequence in vitro. In C1ql2/3 double-null mice, CA3 synaptic responses lost the slow, KAR-mediated components. Furthermore, despite induction of MF sprouting in a temporal lobe epilepsy model, KARs were not recruited to postsynaptic sites in C1ql2/3 double-null mice, leading to reduced recurrent circuit activities. C1q family proteins, broadly expressed, are likely to modulate KAR function throughout the brain and represent promising antiepileptic targets.
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Both the ADGRB3 receptor (BAI3) and kainate receptors are bound postsynaptically by C1ql proteins, regulating synaptogenesis in the case of ADGRB3 binding and postsynaptic recruitment in the case of kainate receptors.
“Both the ADGRB3 receptor (BAI3) and kainate receptors are bound postsynaptically by C1ql proteins, regulating synaptogenesis in the case of ADGRB3 binding and postsynaptic recruitment in the case of kainate receptors (Sigoillot et al., 2015;Matsuda et al., 2016;Bolliger et al., 2011;Yuzaki, 2017;Martinelli et al., 2016).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Matsuda et al., 2016
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- Authors
- Matsuda, K., Budisantoso, T., Mitakidis, N., Sugaya, Y., Miura, E., Kakegawa, W., Yamasaki, M., Konno, K., Uchigashima, M., Abe, M., Watanabe, I., Kano, M., Watanabe, M., Sakimura, K., Aricescu, A. R., & Yuzaki, M.
- Affiliations
- Keio University (JP)
- Centre for Human Genetics (GB)
- The University of Tokyo (JP)
- Hokkaido University (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Aricescu, A. Radu
- Yuzaki, Michisuke
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 90
- Issue
- 4
- Pages
- 752-767
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2344649716
- Cited by
- 180
- References
- 66
- Citations by year
- 2026: 17 · 2025: 14 · 2024: 19 · 2023: 17 · 2022: 14 · 2021: 15 · 2020: 19 · 2019: 18 · 2018: 15 · 2017: 20 · 2016: 12
- FWCI
- 12.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 382 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- MEXT
- CREST from the JST
- Keio Gijuku Fukuzawa Memorial Fund
- Human Frontier Research Program (RGP0065/2014)
- UK Medical Research Council
- Wellcome Trust (090532/Z/09/Z)
- MRC
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- kainate receptors, mossy fiber-CA3 synapses, hippocampus, GluK2, NRXN3, synaptic clustering, temporal lobe epilepsy
- MeSH terms
- Animals, Hippocampus, Membrane Glycoproteins, Receptors, Complement, Synapses, Pyramidal Cells, Kainic Acid Receptors, Mice, Knockout, Glutamic Acid, Mossy Fibers, Hippocampal, Excitatory Postsynaptic Potentials
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