Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins.
Neuron
; 90(4): 752-67, 2016 05 18.
Article
em En
| MEDLINE
| ID: mdl-27133466
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Receptores de Ácido Caínico
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Células Piramidais
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Fibras Musgosas Hipocampais
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Potenciais Pós-Sinápticos Excitadores
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Hipocampo
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article