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Neuron. 2016 May 18;90(4):752-67. doi: 10.1016/j.neuron.2016.04.001. Epub 2016 Apr 28.

Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins.

Author information

1
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.
2
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
3
Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
4
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.
5
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.
6
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. Electronic address: radu@strubi.ox.ac.uk.
7
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.

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.

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PMID:
27133466
DOI:
10.1016/j.neuron.2016.04.001
[Indexed for MEDLINE]
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