Mechanisms of GABAA receptor assembly and trafficking

Mechanisms of GABAA receptor assembly and trafficking Fast synaptic inhibition in the brain is largely mediated by ionotropic GABA receptors, which can be subdivided into GABAA and GABAC receptors based on pharmacological and molecular criteria. GABAA receptors are important therapeutic targets for a range of sedative, anxiolytic, and hypnotic agents and are implicated in several diseases including epilepsy, anxiety, depression, and substance abuse. In addition, modulating the efficacy of GABAergic neurotransmission may play a key role in neuronal plasticity. Recent studies have begun to reveal that the accumulation of ionotropic GABAA receptors at synapses is a highly regulated process that is facilitated by receptor-associated proteins and other cell-signaling molecules. This review focuses on recent experimental evidence detailing the mechanisms that control the assembly and transport of functional ionotropic GABAA receptors to cell surface sites, in addition to their stability at synaptic sites. These regulatory processes will be discussed within the context of the dynamic modulation of synaptic inhibition in the central nervous system (CNS). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular Neurobiology Springer Journals

Mechanisms of GABAA receptor assembly and trafficking

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Publisher
Springer Journals
Copyright
Copyright © 2002 by Humana Press Inc
Subject
Medicine & Public Health; Neurology; Cell Biology
ISSN
0893-7648
eISSN
1559-1182
DOI
10.1385/MN:26:2-3:251
pmid
12428759
Publisher site
See Article on Publisher Site

Abstract

Fast synaptic inhibition in the brain is largely mediated by ionotropic GABA receptors, which can be subdivided into GABAA and GABAC receptors based on pharmacological and molecular criteria. GABAA receptors are important therapeutic targets for a range of sedative, anxiolytic, and hypnotic agents and are implicated in several diseases including epilepsy, anxiety, depression, and substance abuse. In addition, modulating the efficacy of GABAergic neurotransmission may play a key role in neuronal plasticity. Recent studies have begun to reveal that the accumulation of ionotropic GABAA receptors at synapses is a highly regulated process that is facilitated by receptor-associated proteins and other cell-signaling molecules. This review focuses on recent experimental evidence detailing the mechanisms that control the assembly and transport of functional ionotropic GABAA receptors to cell surface sites, in addition to their stability at synaptic sites. These regulatory processes will be discussed within the context of the dynamic modulation of synaptic inhibition in the central nervous system (CNS).

Journal

Molecular NeurobiologySpringer Journals

Published: May 31, 2007

References

  • Independent assembly and subcellular targeting of GABA(A)-receptor subtypes demonstrated in mouse hippocampal and olfactory neurons in vivo
    Fritschy, J. M.; Johnson, D. K.; Mohler, H.; Rudolph, U.
  • Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors
    Brickley, S. G.; Cull-Candy, S. G.; Farrant, M.
  • Quantal analysis of synaptic potentials in neurons of the central nervous system
    Redman, S.
  • Anatomy and electrophysiology of fast central synapses lead to a structural model for long-term potentiation
    Edwards, F. A.
  • BDNF reduces miniature inhibitory postsynaptic currents by rapid downregulation of GABA(A) receptor surface expression
    Brunig, I.; Penschuck, S.; Berninger, B.; Benson, J.; Fritschy, J. M.
  • Neurotransmitter receptor trafficking and the regulation of synaptic strength
    Kittler, J. T.; Moss, S. J.
  • Interactions of drebrin and gephyrin with profilin
    Mammoto, A.; Sasaki, T.; Asakura, T.
  • GATE-16, a membrane transport modulator, interacts with NSF and the Golgi v-SNARE GOS-28
    Sagiv, Y.; Legesse-Miller, A.; Porat, A.; Elazar, Z.
  • The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABA(A) receptors
    Kittler, J. T.; Rostaing, P.; Schiavo, G.; Fritschy, J. M.; Olsen, R.; Triller, A.; Moss, S. J.
  • LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing
    Kabeya, Y.; Mizushima, N.; Ueno, T.
  • Synaptogenesis: The MAP location of GABA receptors
    Passafaro, M.; Sheng, M.
  • Role of the PLC-related, catalytically inactive protein p130 in GABA(A) receptor function
    Kanematsu, T.; Jang, I. S.; Yamaguchi, T.
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    Mah, A. L.; Perry, G.; Smith, M. A.; Monteiro, M. J.
  • Long-term potentiation of GABAergic synaptic transmission in neonatal rat hippocampus
    Caillard, O.; Ben-Ari, Y.; Gaiarsa, J. L.

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