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GABAA-receptor-associated protein links GABAA receptors and the cytoskeleton

GABAA-receptor-associated protein links GABAA receptors and the cytoskeleton Type-A receptors for the neurotransmitter GABA (γ-aminobutyric acid) are ligand-gated chloride channels that mediate inhibitory neurotransmission. Each subunit of the pentameric receptor protein has ligand-binding sites in the amino-terminal extracellular domain and four membrane-spanning regions, one of which forms a wall of the ion channel 1 . Each subunit also has a large intracellular loop that may be a target for protein kinases and be required for subcellular targeting and membrane clustering of the receptor, perhaps by anchoring the receptor to the cytoskeleton 2,3,4 . Neurotransmitter receptors need to be positioned in high density in the cell membrane at sites postsynaptic to nerve terminals releasing that neurotransmitter. Other members of the superfamily of ligand-gated ion-channel receptors associate in postsynaptic-membrane clusters by binding to the proteins rapsyn or gephyrin 5,6,7 . Here we identify a new cellular protein, GABAA-receptor-associated protein (GABARAP), which can interact with the γ2 subunit of GABAA receptors. GABARAP binds to GABAA receptors both in vitro and in vivo, and co-localizes with the punctate staining of GABAA receptors on cultured cortical neurons. Sequence analysis shows similarity between GABARAP and light chain-3 of microtubule-associated proteins 1A and 1B. Moreover, the N terminus of GABARAP is highly positively charged and features a putative tubulin-binding motif. The interactions among GABAA receptors, GABARAP and tubulin suggest a mechanism for the targeting and clustering of GABAA receptors. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

GABAA-receptor-associated protein links GABAA receptors and the cytoskeleton

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References (27)

Publisher
Springer Journals
Copyright
Copyright © 1999 by Macmillan Magazines Ltd.
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
DOI
10.1038/16264
Publisher site
See Article on Publisher Site

Abstract

Type-A receptors for the neurotransmitter GABA (γ-aminobutyric acid) are ligand-gated chloride channels that mediate inhibitory neurotransmission. Each subunit of the pentameric receptor protein has ligand-binding sites in the amino-terminal extracellular domain and four membrane-spanning regions, one of which forms a wall of the ion channel 1 . Each subunit also has a large intracellular loop that may be a target for protein kinases and be required for subcellular targeting and membrane clustering of the receptor, perhaps by anchoring the receptor to the cytoskeleton 2,3,4 . Neurotransmitter receptors need to be positioned in high density in the cell membrane at sites postsynaptic to nerve terminals releasing that neurotransmitter. Other members of the superfamily of ligand-gated ion-channel receptors associate in postsynaptic-membrane clusters by binding to the proteins rapsyn or gephyrin 5,6,7 . Here we identify a new cellular protein, GABAA-receptor-associated protein (GABARAP), which can interact with the γ2 subunit of GABAA receptors. GABARAP binds to GABAA receptors both in vitro and in vivo, and co-localizes with the punctate staining of GABAA receptors on cultured cortical neurons. Sequence analysis shows similarity between GABARAP and light chain-3 of microtubule-associated proteins 1A and 1B. Moreover, the N terminus of GABARAP is highly positively charged and features a putative tubulin-binding motif. The interactions among GABAA receptors, GABARAP and tubulin suggest a mechanism for the targeting and clustering of GABAA receptors.

Journal

NatureSpringer Journals

Published: Jan 7, 1999

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