title: Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins.
abstract: 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.
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan.
authors.forename: Timotheus
authors.initials: T
authors.lastname: Budisantoso
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Mitakidis
authors.affiliation: Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugaya
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Miura
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kakegawa
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan; Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan; Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Kohtarou
authors.initials: K
authors.lastname: Konno
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan; Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Motokazu
authors.initials: M
authors.lastname: Uchigashima
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan; Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Abe
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan; Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Watanabe
authors.affiliation: Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan; Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan; Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. Electronic address: radu@strubi.ox.ac.uk.
authors.forename: A Radu
authors.initials: AR
authors.lastname: Aricescu
authors.affiliation: Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan. Electronic address: myuzaki@a5.keio.jp.
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism*; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; D018092:Kainic Acid Receptors; C032402:complement 1q receptor