JBC PeproTech; Our Business is Cytokines!

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M011054200 on January 2, 2001

J. Biol. Chem., Vol. 276, Issue 13, 10532-10538, March 30, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/13/10532    most recent
M011054200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tretter, V.
Right arrow Articles by Sieghart, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tretter, V.
Right arrow Articles by Sieghart, W.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Targeted Disruption of the GABAA Receptor delta  Subunit Gene Leads to an Up-regulation of gamma 2 Subunit-containing Receptors in Cerebellar Granule Cells*

Verena TretterDagger §, Birgit HauerDagger §, Zoltan Nusser||, Robert M. Mihalek**, Harald HögerDagger Dagger , Gregg E. Homanics**, Peter Somogyi, and Werner SieghartDagger §§

From the Dagger  University Clinic for Psychiatry, Section of Biochemical Psychiatry and Brain Research Institute of the University of Vienna, Vienna A-1090, Austria, the  Medical Research Council, Anatomical Neuropharmacology Unit, Oxford OX1 3TH, United Kingdom, the ** Departments of Anesthesiology/Critical Care Medicine and Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and the Dagger Dagger  Research Institute for Laboratory Animal Breeding, Himberg A-2325, Austria

GABAA receptors are chloride channels composed of five subunits. Cerebellar granule cells express abundantly six subunits belonging to four subunit classes. These are assembled into a number of distinct receptors, but the regulation of their relative proportions is yet unknown. Here, we studied the composition of cerebellar GABAA receptors after targeted disruption of the delta  subunit gene. In membranes and extracts of delta -/- cerebellum, [3H]muscimol binding was not significantly changed, whereas [3H]Ro15-4513 binding was increased by 52% due to an increase in diazepam-insensitive binding. Immunocytochemical and Western blot analysis revealed no change in alpha 6 subunits but an increased expression of gamma 2 subunits in delta -/- cerebellum. Immunoaffinity chromatography of cerebellar extracts indicated there was an increased coassembly of alpha 6 and gamma 2 subunits and that 24% of all receptors in delta -/- cerebellum did not contain a gamma  subunit. Because 97% of delta  subunits are coassembled with alpha 6 subunits in the cerebellum of wild-type mice, these results indicated that, in delta -/- mice, alpha 6beta gamma 2 and alpha beta receptors replaced delta  subunit-containing receptors. The availability of the delta  subunit, thus, influences the level of expression or the extent of assembly of the gamma 2 subunit, although these two subunits do not occur in the same receptor.

* This study was supported by a European Commission Shared Cost RTD Programme Grant (ERBBIO4CT960585) and by National Institutes of Health Grants AA10422 and GM52035.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Both authors contributed equally to this work.

|| Present address: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1450, Hungary.

§§ To whom correspondence should be addressed: Brain Research Institute of the University of Vienna, Spitalgasse 4, Vienna A-1090, Austria. Tel.: 43-1-4277-62950; Fax: 43-1-4277-62959, E-mail: Werner.Sieghart@univie.ac.at.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Neurosci.Home page
N. Zhang, W. Wei, I. Mody, and C. R. Houser
Altered Localization of GABAA Receptor Subunits on Dentate Granule Cell Dendrites Influences Tonic and Phasic Inhibition in a Mouse Model of Epilepsy
J. Neurosci., July 11, 2007; 27(28): 7520 - 7531.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
S. H. Hadley and J. Amin
Rat {alpha}6beta2{delta} GABAA receptors exhibit two distinct and separable agonist affinities
J. Physiol., June 15, 2007; 581(3): 1001 - 1018.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
M. Mortensen and T. G. Smart
Extrasynaptic {alpha}{beta} subunit GABAA receptors on rat hippocampal pyramidal neurons
J. Physiol., December 15, 2006; 577(3): 841 - 856.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. Chandra, F. Jia, J. Liang, Z. Peng, A. Suryanarayanan, D. F. Werner, I. Spigelman, C. R. Houser, R. W. Olsen, N. L. Harrison, et al.
GABAA receptor {alpha}4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol
PNAS, October 10, 2006; 103(41): 15230 - 15235.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
J. H. Krystal, J. Staley, G. Mason, I. L. Petrakis, J. Kaufman, R. A. Harris, J. Gelernter, and J. Lappalainen
{gamma}-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment.
Arch Gen Psychiatry, September 1, 2006; 63(9): 957 - 968.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
Z. Peng, C. S. Huang, B. M. Stell, I. Mody, and C. R. Houser
Altered Expression of the {delta} Subunit of the GABAA Receptor in a Mouse Model of Temporal Lobe Epilepsy
J. Neurosci., September 29, 2004; 24(39): 8629 - 8639.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. M. Stell, S. G. Brickley, C. Y. Tang, M. Farrant, and I. Mody
Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by {delta} subunit-containing GABAA receptors
PNAS, November 25, 2003; 100(24): 14439 - 14444.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
W. Wei, N. Zhang, Z. Peng, C. R. Houser, and I. Mody
Perisynaptic Localization of {delta} Subunit-Containing GABAA Receptors and Their Activation by GABA Spillover in the Mouse Dentate Gyrus
J. Neurosci., November 19, 2003; 23(33): 10650 - 10661.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
I. Spigelman, Z. Li, J. Liang, E. Cagetti, S. Samzadeh, R. M. Mihalek, G. E. Homanics, and R. W. Olsen
Reduced Inhibition and Sensitivity to Neurosteroids in Hippocampus of Mice Lacking the GABAA Receptor {delta} Subunit
J Neurophysiol, August 1, 2003; 90(2): 903 - 910.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Bollan, D. King, L. A. Robertson, K. Brown, P. M. Taylor, S. J. Moss, and C. N. Connolly
GABAA Receptor Composition Is Determined by Distinct Assembly Signals within alpha and beta Subunits
J. Biol. Chem., February 7, 2003; 278(7): 4747 - 4755.
[Abstract] [Full Text] [PDF]

Home page
 J Child NeurolHome page
T. A. Simeone, S. D. Donevan, and J. M. Rho
Molecular Biology and Ontogeny of {gamma}-Aminobutyric Acid (GABA) Receptors in the Mammalian Central Nervous System
J Child Neurol, January 1, 2003; 18(1): 39 - 48.
[Abstract] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.