GABAB-receptor subtypes assemble into functional heteromeric complexes

Klemens Kaupmann, Barbara Malitschek, Valerie Schuler, Jakob Heid, Wolfgang Froestl, Pascal Beck, Johannes Mosbacher, Serge Bischoff, Akos Kulik, Ryuichi Shigemoto, Andreas Karschin and Bernhard Bettler ()
Additional contact information
Klemens Kaupmann: Novartis Pharma AG, TA Nervous System
Barbara Malitschek: Novartis Pharma AG, TA Nervous System
Valerie Schuler: Novartis Pharma AG, TA Nervous System
Jakob Heid: Novartis Pharma AG, TA Nervous System
Wolfgang Froestl: Novartis Pharma AG, TA Nervous System
Pascal Beck: Novartis Pharma AG, TA Nervous System
Johannes Mosbacher: Novartis Pharma AG, TA Nervous System
Serge Bischoff: Novartis Pharma AG, TA Nervous System
Akos Kulik: Faculty of Medicine, Kyoto University
Ryuichi Shigemoto: Faculty of Medicine, Kyoto University
Andreas Karschin: Molecular Neurobiology of Signal Transduction, Max-Planck-Institute for Biophysical Chemistry
Bernhard Bettler: Novartis Pharma AG, TA Nervous System

Nature, 1998, vol. 396, issue 6712, 683-687

Abstract: Abstract B-type receptors for the neurotransmitter GABA (γ-aminobutyric acid) inhibit neuronal activity through G-protein-coupled second-messenger systems, which regulate the release of neurotransmitters and the activity of ion channels and adenylyl cyclase1. Physiological and biochemical studies show that there are differences in drug efficiencies at different GABAB receptors, so it is expected that GABAB-receptor (GABABR) subtypes exist2. Two GABAB-receptor splice variants have been cloned3 (GABABR1a and GABABR1b), but native GABAB receptors and recombinant receptors showed unexplained differences in agonist-binding potencies. Moreover, the activation of presumed effector ion channels in heterologous cells expressing the recombinant receptors proved difficult3,4. Here we describe a new GABAB receptor subtype, GABABR2, which does not bind available GABAB antagonists with measurable potency. GABABR1a, GABABR1b and GABABR2 alone do not activate Kir3-type potassium channels efficiently, but co-expression of these receptors yields a robust coupling to activation of Kir3 channels. We provide evidence for the assembly of heteromeric GABAB receptors in vivo and show that GABABR2 and GABABR1a/b proteins immunoprecipitate and localize together at dendritic spines. The heteromeric receptor complexes exhibit a significant increase in agonist- and partial-agonist-binding potencies as compared with individual receptors and probably represent the predominant native GABAB receptor. Heteromeric assembly among G-protein-coupled receptors has not, to our knowledge, been described before.

Date: 1998
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/25360 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:396:y:1998:i:6712:d:10.1038_25360

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/25360

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().