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- Title
Sustained Structural Change of GABA<sub>A</sub> Receptor-Associated Protein Underlies Long-Term Potentiation at Inhibitory Synapses on a Cerebellar Purkinje Neuron.
- Authors
Kawaguchi, Shin-ya; Hirano, Tomoo
- Abstract
Fast inhibitory synaptic transmission is predominantly mediated by GABAA receptor (GABAAR) in the CNS. Although several types of neuronal activity-dependent plasticity at GABAergic synapses have been reported, the detailed mechanism is elusive. Here we show that binding of structurally altered GABAAR-associated protein (GABARAP) to GABAARγ2 subunit and to tubulin is critical for long-term potentiation [called rebound potentiation (RP)] at inhibitory synapses on a cerebellar Purkinje neuron (PN). Either inhibition of GABARAP association with GABAARγ2 or deletion of tubulin binding region of GABARAP impaired RP. Inhibition of tubulin polymerization also suppressed RP. Thus, precise regulation of GABAARγ2-GABARAP-microtubule interaction is critical for RP. Furthermore, competitive inhibition of GABARAP binding to GABAARγ2 after the RP establishment attenuated the potentiated response, suggesting that GABARAP is critical not only for the induction but also for the maintenance of RP. Fluorescence resonance energy transfer analysis revealed that GABARAP underwent sustained structural alteration after brief depolarization of a PN depending on the activity of Ca2+/ calmodulin-dependent protein kinase II (CaMKII), which is required for the RP induction. The susceptibility of GABARAP to undergo structural alteration was abolished by an amino acid replacement in GABARAP. Furthermore, RP was impaired by expression of the mutant GABARAP with the replacement. Together, we conclude that GABAAR association with structurally altered GABARAP downstream of CaMKII activation is essential for RP.
- Subjects
GABA; NEURAL transmission; NEURAL circuitry; TUBULINS; CALMODULIN; POLYMERIZATION; PROTEIN kinases
- Publication
Journal of Neuroscience, 2007, Vol 27, Issue 25, p6788
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1981-07.2007