RRC ID |
37886
|
著者 |
Bannai H, Niwa F, Sherwood MW, Shrivastava AN, Arizono M, Miyamoto A, Sugiura K, Lévi S, Triller A, Mikoshiba K.
|
タイトル |
Bidirectional Control of Synaptic GABAAR Clustering by Glutamate and Calcium.
|
ジャーナル |
Cell Rep
|
Abstract |
GABAergic synaptic transmission regulates brain function by establishing the appropriate excitation-inhibition (E/I) balance in neural circuits. The structure and function of GABAergic synapses are sensitive to destabilization by impinging neurotransmitters. However, signaling mechanisms that promote the restorative homeostatic stabilization of GABAergic synapses remain unknown. Here, by quantum dot single-particle tracking, we characterize a signaling pathway that promotes the stability of GABAA receptor (GABAAR) postsynaptic organization. Slow metabotropic glutamate receptor signaling activates IP3 receptor-dependent calcium release and protein kinase C to promote GABAAR clustering and GABAergic transmission. This GABAAR stabilization pathway counteracts the rapid cluster dispersion caused by glutamate-driven NMDA receptor-dependent calcium influx and calcineurin dephosphorylation, including in conditions of pathological glutamate toxicity. These findings show that glutamate activates distinct receptors and spatiotemporal patterns of calcium signaling for opposing control of GABAergic synapses.
|
巻・号 |
13(12)
|
ページ |
2768-80
|
公開日 |
2015-12-29
|
DOI |
10.1016/j.celrep.2015.12.002
|
PII |
S2211-1247(15)01414-X
|
PMID |
26711343
|
PMC |
PMC4700050
|
MeSH |
Animals
Calcium / metabolism*
Calcium Signaling
GABAergic Neurons / metabolism
GABAergic Neurons / physiology*
Glutamic Acid / metabolism*
Mice, Knockout
Rats
Rats, Wistar
Receptors, GABA-A / metabolism*
Synaptic Transmission / physiology*
|
IF |
8.109
|
引用数 |
44
|
WOS 分野
|
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
HeLa(RCB0007) |