DOI: 10.1523/jneurosci.3277-07.2007. Activity-Dependent Ubiquitination of GABA<sub>A</sub>Receptors Regulates Their Accumulation at Synaptic Sites

Activity-Dependent Ubiquitination of GABAAReceptors Regulates Their Accumulation at Synaptic Sites

10.1523/jneurosci.3277-07.2007

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

GABAAreceptors (GABAARs) are the major mediators of fast synaptic inhibition in the brain. In neurons, these receptors undergo significant rates of endocytosis and exocytosis, processes that regulate both their accumulation at synaptic sites and the efficacy of synaptic inhibition. Here we have evaluated the role that neuronal activity plays in regulating the residence time of GABAARs on the plasma membrane and their targeting to synapses. Chronic blockade of neuronal activity dramatically increases the level of the GABAAR ubiquitination, decreasing their cell surface stability via a mechanism dependent on the activity of the proteasome. Coincident with this loss of cell surface expression levels, TTX treatment reduced both the amplitude and frequency of miniature inhibitory synaptic currents. Conversely, increasing the level of neuronal activity decreases GABAAR ubiquitination enhancing their stability on the plasma membrane. Activity-dependent ubiquitination primarily acts to reduce GABAAR stability within the endoplasmic reticulum and, thereby, their insertion into the plasma membrane and subsequent accumulation at synaptic sites. Thus, activity-dependent ubiquitination of GABAARs and their subsequent proteasomal degradation may represent a potent mechanism to regulate the efficacy of synaptic inhibition and may also contribute to homeostatic synaptic plasticity.

Bibliography

Saliba, R. S., Michels, G., Jacob, T. C., Pangalos, M. N., & Moss, S. J. (2007). Activity-Dependent Ubiquitination of GABAAReceptors Regulates Their Accumulation at Synaptic Sites. The Journal of Neuroscience, 27(48), 13341â13351.

Authors 5

Richard S. Saliba (first)
Guido Michels (additional)
Tija C. Jacob (additional)
Menelas N. Pangalos (additional)
Stephen J. Moss (additional)

References 50 Referenced 107

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Dates

Type	When
Created	17 years, 9 months ago (Nov. 28, 2007, 12:28 p.m.)
Deposited	2 years, 4 months ago (April 13, 2023, 2:25 p.m.)
Indexed	6 hours, 40 minutes ago (Sept. 2, 2025, 6:39 a.m.)
Issued	17 years, 9 months ago (Nov. 28, 2007)
Published	17 years, 9 months ago (Nov. 28, 2007)
Published Online	17 years, 9 months ago (Nov. 28, 2007)
Published Print	17 years, 9 months ago (Nov. 28, 2007)

Funders 0

None

BibTeX

@article{Saliba_2007, title={Activity-Dependent Ubiquitination of GABAAReceptors Regulates Their Accumulation at Synaptic Sites}, volume={27}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.3277-07.2007}, DOI={10.1523/jneurosci.3277-07.2007}, number={48}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Saliba, Richard S. and Michels, Guido and Jacob, Tija C. and Pangalos, Menelas N. and Moss, Stephen J.}, year={2007}, month=nov, pages={13341–13351} }

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