Complex role of collybistin and gephyrin in GABAA receptor clustering.

The Journal of Biological Chemistry
Leila SaiepourKirsten Harvey

Abstract

Gephyrin and collybistin are key components of GABA(A) receptor (GABA(A)R) clustering. Nonetheless, resolving the molecular interactions between the plethora of GABA(A)R subunits and these clustering proteins is a significant challenge. We report a direct interaction of GABA(A)R α2 and α3 subunit intracellular M3-M4 domain (but not α1, α4, α5, α6, β1-3, or γ1-3) with gephyrin. Curiously, GABA(A)R α2, but not α3, binds to both gephyrin and collybistin using overlapping sites. The reciprocal binding sites on gephyrin for collybistin and GABA(A)R α2 also overlap at the start of the gephyrin E domain. This suggests that although GABA(A)R α3 interacts with gephyrin, GABA(A)R α2, collybistin, and gephyrin form a trimeric complex. In support of this proposal, tri-hybrid interactions between GABA(A)R α2 and collybistin or GABA(A)R α2 and gephyrin are strengthened in the presence of gephyrin or collybistin, respectively. Collybistin and gephyrin also compete for binding to GABA(A)R α2 in co-immunoprecipitation experiments and co-localize in transfected cells in both intracellular and submembrane aggregates. Interestingly, GABA(A)R α2 is capable of "activating " collybistin isoforms harboring the regulatory SH3 domain, enabling targeting...Continue Reading

References

Jul 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·M KneusselH Betz
Jun 21, 2001·Molecular and Cellular Neurosciences·M KneusselH Betz
Jun 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·F CrestaniU Rudolph
Nov 20, 2002·Journal of Neurochemistry·Jesper Nymann-AndersenRichard W Olsen
Oct 24, 2003·Molecular and Cellular Neurosciences·Claude SchweizerBernhard Lüscher
Jan 13, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sabine LéviAnn Marie Craig
Jun 25, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kirsten HarveyRobert J Harvey
Jan 22, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Melissa J AlldredBernhard Lüscher
Mar 3, 2006·The EMBO Journal·Eun Young KimHermann Schindelin
Sep 26, 2006·The Journal of Comparative Neurology·David R SerwanskiAngel L De Blas
Dec 8, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cheng FangBernhard Lüscher
Oct 6, 2007·Molecular and Cellular Neurosciences·Wendou YuAngel L de Blas
Feb 8, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Verena TretterStephen J Moss
Apr 12, 2008·Trends in Neurosciences·Jean-Marc FritschyGünter Schwarz
Jul 16, 2008·Molecular and Cellular Neurosciences·Theofilos PapadopoulosHeinrich Betz
Aug 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Annarita PatriziMarco Sassoè-Pognetto
Jun 26, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mrinalini HoonFrédérique Varoqueaux
Jul 25, 2009·Human Molecular Genetics·Rosa M SanchoKirsten Harvey
Oct 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Delia BelelliDavid W Cope
Nov 17, 2009·Biochemical Society Transactions·Hanns Möhler
Nov 20, 2009·Frontiers in Molecular Neuroscience·Heinz WässleSilke Haverkamp
Dec 5, 2009·The Journal of Biological Chemistry·Nima MelzerCord-Michael Becker

❮ Previous
Next ❯

Citations

Jun 19, 2013·Experimental Cell Research·Wei BaNael Nadif Kasri
Nov 23, 2011·Journal of Proteome Research·A KantardzhievaW F Sewell
Sep 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Rochelle M HinesStephen J Moss
Sep 2, 2011·The Journal of Biological Chemistry·Verena TretterKirsten Harvey
Oct 19, 2011·The Journal of Biological Chemistry·Hans-Michael MaricHermann Schindelin
Sep 23, 2010·BMC Research Notes·Andrea L SertieMaria Rita Passos-Bueno
Jul 7, 2012·PloS One·Elizabeth A HellerNathaniel Heintz
Oct 14, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jayanta MukherjeeStephen J Moss
Dec 4, 2013·Proceedings of the National Academy of Sciences of the United States of America·Simone MayerTheofilos Papadopoulos
Dec 22, 2010·Proceedings of the National Academy of Sciences of the United States of America·Shiva K TyagarajanJean-Marc Fritschy
Apr 22, 2014·Molecular and Cellular Neurosciences·K Gerrow, A Triller
Dec 4, 2014·Molecular and Cellular Neurosciences·Géraldine GouzerAntoine Triller
Feb 9, 2012·Cellular and Molecular Life Sciences : CMLS·Jean-Marc FritschyShiva K Tyagarajan
Mar 15, 2016·Frontiers in Cellular Neuroscience·Yudong Gao, Scott A Heldt
Apr 23, 2015·European Journal of Human Genetics : EJHG·Camila Oliveira Freitas MachadoAndrea Laurato Sertie
May 2, 2014·Frontiers in Cellular Neuroscience·Paola ZacchiEnrico Cherubini
Jul 8, 2014·Frontiers in Cellular Neuroscience·Marta Pallotto, Francine Deprez
Nov 1, 2011·Current Opinion in Neurobiology·Rochelle M HinesJamie Maguire
Jun 5, 2012·Molecular and Cellular Neurosciences·Christoph KörberJochen Kuhse
Nov 3, 2016·The Journal of Comparative Neurology·Christopher D FeketeAngel L De Blas
Apr 18, 2015·Experimental & Molecular Medicine·Gayoung Choii, Jaewon Ko
Apr 10, 2018·Experimental & Molecular Medicine·Olga BabaevDilja Krueger-Burg
Sep 16, 2018·Proteins·B W J IrwinP-L Chau
Feb 19, 2019·The Journal of Comparative Neurology·Ida Luisa BoccalaroLena Rubi
Feb 21, 2014·Nature Reviews. Neuroscience·Shiva K Tyagarajan, Jean-Marc Fritschy
May 18, 2011·The Journal of Biological Chemistry·Martin KriebelHansjürgen Volkmer
Mar 6, 2012·The Journal of Biological Chemistry·Isabella Sarto-JacksonWerner Sieghart
Dec 5, 2012·The European Journal of Neuroscience·Sarah KowalczykJochen C Meier
Aug 29, 2013·The Journal of Comparative Neurology·Alexander E LinsalataThomas S Reese
Jan 16, 2014·The Journal of Biological Chemistry·Christine DixonAngelo Keramidas

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.