RIC-3 Affects Properties and Quantity of Nicotinic Acetylcholine Receptors via a Mechanism That Does Not Require the Coiled-coil Domains
| Autor: | Avner Michaeli, Hagit Cohen Ben-Ami, Margalit Eshel, Millet Treinin, Lina Yassin, Hanna Farah |
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| Rok vydání: | 2005 |
| Předmět: |
DNA
Complementary Time Factors genetic structures Xenopus Blotting Western Green Fluorescent Proteins Molecular Sequence Data Receptors Nicotinic Biology Biochemistry Choline RNA Complementary Xenopus laevis Cytosol hemic and lymphatic diseases Animals Humans Immunoprecipitation Protein Isoforms Amino Acid Sequence Caenorhabditis elegans Caenorhabditis elegans Proteins Receptor Molecular Biology Acetylcholine receptor Dose-Response Relationship Drug Sequence Homology Amino Acid Cell Membrane Cell Biology biology.organism_classification Protein Structure Tertiary Cell biology Electrophysiology Kinetics Nicotinic acetylcholine receptor Transmembrane domain Nicotinic agonist Mutation Oocytes sense organs Heterologous expression Alpha-4 beta-2 nicotinic receptor Gene Deletion Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 280:28053-28060 |
| ISSN: | 0021-9258 |
| Popis: | Members of the RIC-3 gene family are effectors of nicotinic acetylcholine receptor (nAChR) expression in vertebrates and invertebrates. In Caenorhabditis elegans RIC-3 is needed for functional expression of multiple nAChRs, including the DEG-3/DES-2 nAChR. Effects of RIC-3 on DEG-3/DES-2 functional expression are found in vivo and following heterologous expression in Xenopus leavis oocytes. We now show that in X. leavis oocytes RIC-3 also affects the kinetics and agonist affinity properties of the DEG-3/DES-2 receptor. Because these effects are mimicked by increasing the ratio of DEG-3 subunits within DEG-3/DES-2 receptors, this suggests that RIC-3 may preferentially promote maturation of DEG-3-rich receptors. Indeed, effects of RIC-3 on functional expression of DEG-3/DES-2 positively correlate with the DEG-3 to DES-2 ratio. All RIC-3 family members have two transmembrane domains followed by one or two coiled-coil domains. Here we show that the effects of RIC-3 on functional expression and on receptor properties are mediated by the transmembrane domains and do not require the coiled-coil domains. In agreement with this, mammals express a RIC-3 transcript lacking the coiled-coil domain that is capable of promoting DEG-3/DES-2 functional expression. Last, we show that RIC-3 affects DEG-3 quantity, suggesting stabilization of receptors or receptor intermediates by RIC-3. Together our results suggest that subunit-specific interactions of RIC-3 with nAChR subunits, mediated by the transmembrane domains, are sufficient for the effects of RIC-3 on nAChR quantity and quality. |
| Databáze: | OpenAIRE |
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