Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins
| Autor: | Yuki Sugaya, Keiko Matsuda, Manabu Abe, Nikolaos Mitakidis, Masanobu Kano, Kenji Sakimura, Miwako Yamasaki, A. Radu Aricescu, Kohtarou Konno, Izumi Watanabe, Wataru Kakegawa, Michisuke Yuzaki, Motokazu Uchigashima, Masahiko Watanabe, Timotheus Budisantoso, Eriko Miura |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Mossy fiber (hippocampus) Glutamic Acid Hippocampus Kainate receptor Biology Inhibitory postsynaptic potential 03 medical and health sciences 0302 clinical medicine Receptors Kainic Acid Postsynaptic potential Animals Mice Knockout Membrane Glycoproteins Pyramidal Cells General Neuroscience Glutamate receptor Excitatory Postsynaptic Potentials Receptors Complement 030104 developmental biology Mossy Fibers Hippocampal Synapses Excitatory postsynaptic potential Postsynaptic density Neuroscience 030217 neurology & neurosurgery |
| DOI: | 10.1016/j.neuron.2016.04.001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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