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Science 1 January 1999:
Vol. 283. no. 5398, pp. 74 - 77
DOI: 10.1126/science.283.5398.74
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Reports

Role of Heteromer Formation in GABAB Receptor Function

Rohini Kuner, Georg Köhr, Sylvia Grünewald, Gisela Eisenhardt, Alfred Bach, Hans-Christian Kornau *

Recently, GBR1, a seven-transmembrane domain protein with high affinity for gamma -aminobutyric acid (GABA)B receptor antagonists, was identified. Here, a GBR1-related protein, GBR2, was shown to be coexpressed with GBR1 in many brain regions and to interact with it through a short domain in the carboxyl-terminal cytoplasmic tail. Heterologously expressed GBR2 mediated inhibition of adenylyl cyclase; however, inwardly rectifying potassium channels were activated by GABAB receptor agonists only upon coexpression with GBR1 and GBR2. Thus, the interaction of these receptors appears to be crucial for important physiological effects of GABA and provides a mechanism in receptor signaling pathways that involve a heterotrimeric GTP-binding protein.

R. Kuner, S. Grünewald, G. Eisenhardt, A. Bach, H.-C. Kornau, BASF-LYNX Bioscience AG, Department of Neuroscience, Im Neuenheimer Feld 515, D-69120 Heidelberg, Germany. G. Köhr, Max-Planck-Institute for Medical Research, Department of Molecular Neurobiology, Jahnstrasse 29, D-69120 Heidelberg, Germany.
*   To whom correspondence should be addressed. E-mail: kornau{at}basf-lynx.de

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The CB1 Cannabinoid Receptor Juxtamembrane C-Terminal Peptide Confers Activation to Specific G proteins in Brain.
S. Mukhopadhyay, H. H. McIntosh, D. B. Houston, and A. C. Howlett (2000)
Mol. Pharmacol. 57, 162-170
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Functional Characterization of Mutations in Melanocortin-4 Receptor Associated with Human Obesity.
G. Ho and R. G. MacKenzie (1999)
J. Biol. Chem. 274, 35816-35822
   Abstract »    Full Text »    PDF »
Probing the Ligand-binding Domain of the mGluR4 Subtype of Metabotropic Glutamate Receptor.
D. R. Hampson, X.-P. Huang, R. Pekhletski, V. Peltekova, G. Hornby, C. Thomsen, and H. Thogersen (1999)
J. Biol. Chem. 274, 33488-33495
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gamma -Aminobutyric Acid Type B Receptor Splice Variant Proteins GBR1a and GBR1b Are Both Associated with GBR2 in Situ and Display Differential Regional and Subcellular Distribution.
D. Benke, M. Honer, C. Michel, B. Bettler, and H. Mohler (1999)
J. Biol. Chem. 274, 27323-27330
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Identification and Characterization of Three New Alternatively Spliced {micro}-Opioid Receptor Isoforms.
Y.-X. Pan, J. Xu, E. Bolan, C. Abbadie, A. Chang, A. Zuckerman, G. Rossi, and G. W. Pasternak (1999)
Mol. Pharmacol. 56, 396-403
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ACCELERATED COMMUNICATION: The N-Terminal Domain of gamma -Aminobutyric AcidB Receptors Is Sufficient to Specify Agonist and Antagonist Binding.
B. Malitschek, C. Schweizer, M. Keir, J. Heid, W. Froestl, J. Mosbacher, R. Kuhn, J. Henley, C. Joly, J.-P. Pin, et al. (1999)
Mol. Pharmacol. 56, 448-454
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Different Subtypes of GABAB Receptors Are Present at Pre- and Postsynaptic Sites Within the Rat Dorsolateral Septal Nucleus.
K. Yamada, B. Yu, and J. P. Gallagher (1999)
J Neurophysiol 81, 2875-2883
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Identification of a GABAB Receptor Subunit, gb2, Required for Functional GABAB Receptor Activity.
G. Y. K. Ng, J. Clark, N. Coulombe, N. Ethier, T. E. Hebert, R. Sullivan, S. Kargman, A. Chateauneuf, N. Tsukamoto, T. McDonald, et al. (1999)
J. Biol. Chem. 274, 7607-7610
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The Metabotropic GABAB Receptor Directly Interacts with the Activating Transcription Factor 4.
R. B. Nehring, H. P. M. Horikawa, O. El Far, M. Kneussel, J. H. Brandstatter, S. Stamm, E. Wischmeyer, H. Betz, and A. Karschin (2000)
J. Biol. Chem. 275, 35185-35191
   Abstract »    Full Text »    PDF »
Identification of an Essential Amino Acid Motif within the C Terminus of the Pituitary Adenylate Cyclase-activating Polypeptide Type I Receptor That Is Critical for Signal Transduction but Not for Receptor Internalization.
R.-M. Lyu, P. M. Germano, J. K. Choi, S. V. Le, and J. R. Pisegna (2000)
J. Biol. Chem. 275, 36134-36142
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Characterization of gamma -Aminobutyric Acid Receptor GABAB(1e), a GABAB(1) Splice Variant Encoding a Truncated Receptor.
D. A. Schwarz, G. Barry, S. D. Eliasof, R. E. Petroski, P. J. Conlon, and R. A. Maki (2000)
J. Biol. Chem. 275, 32174-32181
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Homo- and Heterodimerization of Somatostatin Receptor Subtypes. INACTIVATION OF sst3 RECEPTOR FUNCTION BY HETERODIMERIZATION WITH sst2A.
M. Pfeiffer, T. Koch, H. Schroder, M. Klutzny, S. Kirscht, H.-J. Kreienkamp, V. Hollt, and S. Schulz (2001)
J. Biol. Chem. 276, 14027-14036
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Metabotropic Glutamate 1alpha and Adenosine A1 Receptors Assemble into Functionally Interacting Complexes.
F. Ciruela, M. Escriche, J. Burgueno, E. Angulo, V. Casado, M. M. Soloviev, E. I. Canela, J. Mallol, W.-Y. Chan, C. Lluis, et al. (2001)
J. Biol. Chem. 276, 18345-18351
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Mapping the Agonist-binding Site of GABAB Type 1 Subunit Sheds Light on the Activation Process of GABAB Receptors.
T. Galvez, L. Prezeau, G. Milioti, M. Franek, C. Joly, W. Froestl, B. Bettler, H.-O. Bertrand, J. Blahos, and J.-P. Pin (2000)
J. Biol. Chem. 275, 41166-41174
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Oligomerization of opioid receptors with beta 2-adrenergic receptors: A role in trafficking and mitogen-activated protein kinase activation.
B. A. Jordan, N. Trapaidze, I. Gomes, R. Nivarthi, and L. A. Devi (2001)
PNAS 98, 343-348
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Human receptors for sweet and umami taste.
X. Li, L. Staszewski, H. Xu, K. Durick, M. Zoller, and E. Adler (2002)
PNAS 99, 4692-4696
   Abstract »    Full Text »    PDF »
The role of members of the pertussis toxin-sensitive family of G proteins in coupling receptors to the activation of the G protein-gated inwardly rectifying potassium channel.
J. L. Leaney and A. Tinker (2000)
PNAS 97, 5651-5656
   Abstract »    Full Text »    PDF »
Heteromeric association creates a P2Y-like adenosine receptor.
K. Yoshioka, O. Saitoh, and H. Nakata (2001)
PNAS 98, 7617-7622
   Abstract »    Full Text »    PDF »


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