A conserved Cys-loop receptor aspartate residue in the M3-M4 cytoplasmic loop is required for GABAA receptor assembly.

The Journal of Biological Chemistry
Wen-Yi LoRobert L Macdonald

Abstract

Members of the Cys-loop superfamily of ligand-gated ion channels, which mediate fast synaptic transmission in the nervous system, are assembled as heteropentamers from a large repertoire of neuronal subunits. Although several motifs in subunit N-terminal domains are known to be important for subunit assembly, increasing evidence points toward a role for C-terminal domains. Using a combination of flow cytometry, patch clamp recording, endoglycosidase H digestion, brefeldin A treatment, and analytic centrifugation, we identified a highly conserved aspartate residue at the boundary of the M3-M4 loop and the M4 domain that was required for binary and ternary gamma-aminobutyric acid type A receptor surface expression. Mutation of this residue caused mutant and partnering subunits to be retained in the endoplasmic reticulum, reflecting impaired forward trafficking. Interestingly although mutant and partnering wild type subunits could be coimmunoprecipitated, analytic centrifugation studies demonstrated decreased formation of pentameric receptors, suggesting that this residue played an important role in later steps of subunit oligomerization. We thus conclude that C-terminal motifs are also important determinants of Cys-loop receptor ...Continue Reading

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Citations

Jul 20, 2010·The Journal of Biological Chemistry·Wen-Yi LoRobert L Macdonald
Sep 10, 2011·The Journal of Biological Chemistry·Kate K O'Toole, Andrew Jenkins
May 15, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alan S LewisDane M Chetkovich
Oct 15, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jing-Qiong KangRobert L Macdonald
Dec 2, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Matthew D Rannals, Jaideep Kapur
Jan 11, 2011·Trends in Cell Biology·Omar A Ramírez, Andrés Couve
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Oct 13, 2017·Journal of Neurochemistry·Andrea N Beltrán GonzálezDaniel J Calvo
Jan 11, 2011·Journal of Neurochemistry·Victor TsetlinIgor Kasheverov
Oct 30, 2016·Journal of Medical Genetics·Atsushi IshiiShinichi Hirose
May 5, 2020·ACS Chemical Neuroscience·Ana R G M da Costa CoutoSarah C R Lummis
Dec 10, 2020·ACS Chemical Neuroscience·Susanne M Mesoy, Sarah C R Lummis
Oct 13, 2021·Current Biology : CB·Alex J Yu, Catharine H Rankin

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