Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Excitatory Postsynaptic Potentials / physiology*
  • Glutamic Acid / metabolism
  • Hippocampus / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice, Knockout
  • Mossy Fibers, Hippocampal / metabolism*
  • Pyramidal Cells / metabolism*
  • Receptors, Complement / genetics
  • Receptors, Complement / metabolism
  • Receptors, Kainic Acid / metabolism*
  • Synapses / genetics
  • Synapses / metabolism*


  • Membrane Glycoproteins
  • Receptors, Complement
  • Receptors, Kainic Acid
  • complement 1q receptor
  • Glutamic Acid