Journal article
Multifunctional basic motif in the glycine receptor intracellular domain induces subunit-specific sorting
Journal of Biological Chemistry, Vol.285(6), pp.3730-3739
2010
Abstract
The strychnine-sensitive glycine receptor (GlyR) is a ligand-gated ion channel that mediates fast synaptic inhibition in the vertebrate central nervous system. As a member of the family of Cys-loop receptors, it assembles from five homologous subunits (GlyRα1-4 and -β). Each subunit contains an extracellular ligand binding domain, four transmembrane domains (TM), and an intracellular domain, formed by the loop connecting TM3 and TM4 (TM3-4 loop). The TM3-4 loops of the subunits GlyRα1 and -α3 harbor a conserved basic motif, which is part of a potential nuclear localization signal. When tested for functionality by live cell imaging of green fluorescent protein and β-galactosidase-tagged domain constructs, the TM3-4 loops of GlyRα1 and -α3, but not of GlyRα2 and -β, exhibited nuclear sorting activity. Subunit specificity may be attributed to slight amino acid alterations in the basic motif. In yeast two-hybrid screening and GST pulldown assays, karyopherin α3 and α4 were found to interact with the TM3-4 loop, providing a molecular mechanism for the observed intracellular trafficking. These results indicate that the multifunctional basic motif of the TM3-4 loop is capable of mediating a karyopherin-dependent intracellular sorting of full-length GlyRs. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Details
- Title
- Multifunctional basic motif in the glycine receptor intracellular domain induces subunit-specific sorting
- Authors
- N Melzer (Author) - Universität Erlangen-Nürnberg, GermanyC Villmann (Author) - Universität Erlangen-Nürnberg, GermanyKristina Becker (Author) - Universität Erlangen-Nürnberg, GermanyK Harvey (Author) - University College London, United KingdomRobert J Harvey (Author) - University College London, United KingdomN Vogel (Author) - Universität Erlangen-Nürnberg, GermanyC J Kluck (Author) - Universität Erlangen-Nürnberg, GermanyM Kneussel (Author) - Universität Hamburg, GermanyC M Becker (Author) - Universität Erlangen-Nürnberg, Germany
- Publication details
- Journal of Biological Chemistry, Vol.285(6), pp.3730-3739
- Publisher
- American Society for Biochemistry and Molecular Biology, Inc.
- Date published
- 2010
- DOI
- 10.1074/jbc.M109.030460
- ISSN
- 0021-9258
- Copyright note
- Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc. The published version is reproduced here in accordance with the publisher's copyright policy.
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99451290302621
- Output Type
- Journal article
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