Glycosylation of {beta}2 subunits regulates GABAA receptor biogenesis and channel gating.

The Journal of Biological Chemistry
Wen-Yi LoRobert L Macdonald

Abstract

γ-aminobutyric acid type A (GABA(A)) receptors are heteropentameric glycoproteins. Based on consensus sequences, the GABA(A) receptor β2 subunit contains three potential N-linked glycosylation sites, Asn-32, Asn-104, and Asn-173. Homology modeling indicates that Asn-32 and Asn-104 are located before the α1 helix and in loop L3, respectively, near the top of the subunit-subunit interface on the minus side, and that Asn-173 is located in the Cys-loop near the bottom of the subunit N-terminal domain. Using site-directed mutagenesis, we demonstrated that all predicted β2 subunit glycosylation sites were glycosylated in transfected HEK293T cells. Glycosylation of each site, however, produced specific changes in α1β2 receptor surface expression and function. Although glycosylation of Asn-173 in the Cys-loop was important for stability of β2 subunits when expressed alone, results obtained with flow cytometry, brefeldin A treatment, and endo-β-N-acetylglucosaminidase H digestion suggested that glycosylation of Asn-104 was required for efficient α1β2 receptor assembly and/or stability in the endoplasmic reticulum. Patch clamp recording revealed that mutation of each site to prevent glycosylation decreased peak α1β2 receptor current ampl...Continue Reading

References

Jan 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·D D Pless, W J Lennarz
Nov 25, 1988·Nucleic Acids Research·F Corpet
Jan 15, 1974·Biochemistry·P Y Chou, G D Fasman
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Apr 1, 1996·Trends in Neurosciences·R M McKernan, P J Whiting
Jan 17, 2003·Nature·Thomas L KashNeil L Harrison
Jun 26, 2003·Nucleic Acids Research·Torsten SchwedeManuel C Peitsch
Nov 12, 2003·The Journal of Biological Chemistry·Thomas L KashNeil L Harrison
Sep 29, 2004·Biochemical Pharmacology·Sarah A MonkNicholas M Barnes
Feb 11, 2005·Journal of Molecular Biology·Nigel Unwin
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
Feb 4, 2006·The Journal of Physiology·Gareth M C Lema, Anthony Auerbach
Oct 7, 2006·The Journal of Physiology·Martin Mortensen, Trevor G Smart
Aug 3, 2007·Proceedings of the National Academy of Sciences of the United States of America·Martin J GallagherRobert L Macdonald
Aug 25, 2007·Clinica Chimica Acta; International Journal of Clinical Chemistry·Eliska Marklová, Ziad Albahri
Apr 9, 2008·Glycobiology·Mari L DeMarco, Robert J Woods
Jun 3, 2008·American Journal of Human Genetics·Miyabi TanakaAntonio V Delgado-Escueta

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Citations

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Aug 7, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Toni Marie MuellerJames H Meador-Woodruff
Aug 5, 2015·Translational Psychiatry·T M MuellerJ H Meador-Woodruff
Jun 10, 2014·Nature·Paul S Miller, A Radu Aricescu
Jul 18, 2019·Expert Review of Proteomics·Danielle A Scott, Richard R Drake
Mar 13, 2014·The Journal of Physiology·Bryan A CopitsGeoffrey T Swanson
Oct 22, 2015·Reviews in the Neurosciences·Ephrem EngidaworkGert Lubec
Jul 18, 2017·The Journal of Physiology·Claire G VernonGeoffrey T Swanson
Mar 8, 2016·Annals of Neurology·Vaishali S JanveRobert L Macdonald
Aug 7, 2021·Molecular & Cellular Proteomics : MCP·Mariana BarbozaCarlito B Lebrilla
May 11, 2011·Neuron·Bernhard LuscherCasey L Kilpatrick

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