+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Climbing fiber-evoked Purkinje cell discharge reduces expression of GABA(A) receptor-associated protein and decreases its interaction with GABA(A) receptors



Climbing fiber-evoked Purkinje cell discharge reduces expression of GABA(A) receptor-associated protein and decreases its interaction with GABA(A) receptors



Journal of Neurochemistry 117(2): 197-208



Sustained neuronal activity induces synaptic remodeling, in part, by altering gene expression. We have used a major climbing fiber pathway onto cerebellar Purkinje cells to investigate the effects of sustained climbing fiber-evoked glutamatergic synaptic transmission on transcription, expression and phosphorylation of proteins related to the regulation of inhibitory GABA(A) receptor function. Binocular horizontal optokinetic stimulation was used to modulate climbing fiber signals to Purkinje cells in the flocculus and nodulus of rabbits and mice. Purkinje cells in the flocculus and nodulus ipsilateral to the eye stimulated in the Posterior→Anterior direction received increased climbing fiber activity. Purkinje cells in flocculus and nodulus ipsilateral to the eye stimulated in the Anterior→Posterior direction received decreased climbing fiber activity. We identified changes in levels of gene transcripts in floccular and nodular Purkinje cells with the technique of differential display RT-PCR. Increased climbing fiber input reduced transcript levels and expression of GABA receptor-associated protein (GABARAP). Using a protein 'pull down' technique, we showed that GABARAP interacts with serine phosphorylated GABA(A)γ2, gephyrin and β-tubulin. Serine de-phosphorylation of GABA(A)γ2 reduced association of GABARAP with GABA(A)γ2. Climbing fiber activity did not influence the expression of GABA(A)γ2. Rather, it decreased its serine phosphorylation. Climbing fiber discharge decreased both expression of GABARAP and serine phosphorylation of GABA(A)γ2. Consequently, climbing fiber activity may reduce the surface expression of GABA(A) receptors in Purkinje cells rendering Purkinje cells less susceptible to interneuronal GABAergic inhibition.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 052101909

Download citation: RISBibTeXText

PMID: 21105873

DOI: 10.1111/j.1471-4159.2010.07119.x


Related references

Climbing fiber activity reduces 14-3-3-θ regulated GABA(A) receptor phosphorylation in cerebellar Purkinje cells. Neuroscience 201: 34-45, 2012

GABA(A) receptor alpha1 subunit mutation A322D associated with autosomal dominant juvenile myoclonic epilepsy reduces the expression and alters the composition of wild type GABA(A) receptors. Journal of Biological Chemistry 285(34): 26390-26405, 2010

Mechanisms of Spontaneous Climbing Fiber Discharge-Evoked Pauses and Output Modulation of Cerebellar Purkinje Cell in Mice. Frontiers in Cellular Neuroscience 11: 247, 2017

Expression of a Drosophila GABA receptor in a baculovirus insect cell system: Functional expression of insecticide susceptible and resistant GABA receptors from the cyclodiene resistance gene Rdl. FEBS (Federation of European Biochemical Societies) Letters 335(3): 315-318, 1993

Serotonin modulation of gaba mediated inhibition on cerebellar purkinje cells involves gaba a and gaba b receptor activation. Society for Neuroscience Abstracts 13(3): 1652, 1987

gamma-Aminobutyric acid (GABA) signaling components in Drosophila: immunocytochemical localization of GABA(B) receptors in relation to the GABA(A) receptor subunit RDL and a vesicular GABA transporter. Journal of Comparative Neurology 505(1): 18-31, 2007

GABA-B but not GABA-A receptors inhibit noxious stimulus-evoked internalization of the neurokinin-1 receptor in rat spinal cord. Society for Neuroscience Abstracts 23(1-2): 447, 1997

Gaba a receptor subunit mrna expression in the deep cerebellar nuclei of the purkinje cell degeneration mutant pcd is unaltered by purkinje cell loss. Society for Neuroscience Abstracts 17(1-2): 78, 1991

Noradrenergic potentiation of cerebellar purkinje cell responses to gaba pharmacologic specificity with respect to adenosine actions and gaba receptor subtypes. Society for Neuroscience Abstracts 14(1): 130, 1988

Expression of GABA(A) and GABA(B) receptors in rat growth plate chondrocytes: activation of the GABA receptors promotes proliferation of mouse chondrogenic ATDC5 cells. Molecular and Cellular Biochemistry 273(1-2): 117-126, 2005

Interaction of carbolines and some GABA receptor ligands with the GABA and the benzodiazepine receptors. Journal de Pharmacologie 17(4): 686-691, 1986

The interaction of a benzodiazepine receptor antagonist (Ro15-1788) with GABA and GABA receptor antagonists at the GABA(A) receptor chloride-ionophore complex. Neurochemistry International 18(3): 405-410, 1991

GABA-noradrenergic interaction: evidence for differential sites of action for GABA-A and GABA-B receptors. Journal of Neural Transmission 64(3-4): 163-172, 1985

GABA-A receptor messenger RNA expression in the deep cerebellar nuclei of Purkinje cell degeneration mutants is maintained following the loss of innervating Purkinje neurons. Neuroscience. 52(1): 63-71, 1993

NMDA receptor activation potentiates inhibitory transmission through GABA receptor-associated protein-dependent exocytosis of GABA(A) receptors. Journal of Neuroscience 27(52): 14326-14337, 2007