Auxiliary GABAB receptor subunits uncouple G protein betagamma subunits from effector channels to induce desensitization

Turecek, Rostislav and Schwenk, Jochen and Fritzius, Thorsten and Ivankova, Klara and Zolles, Gerd and Adelfinger, Lisa and Jacquier, Valérie and Besseyrias, Valérie and Gassmann, Martin and Schulte, Uwe and Fakler, Bernd and Bettler, Bernhard. (2014) Auxiliary GABAB receptor subunits uncouple G protein betagamma subunits from effector channels to induce desensitization. Neuron, 82 (5). pp. 1032-1044.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/61408/

Downloads: Statistics Overview


Activation of K(+) channels by the G protein betagamma subunits is an important signaling mechanism of G-protein-coupled receptors. Typically, receptor-activated K(+) currents desensitize in the sustained presence of agonists to avoid excessive effects on cellular activity. The auxiliary GABAB receptor subunit KCTD12 induces fast and pronounced desensitization of the K(+) current response. Using proteomic and electrophysiological approaches, we now show that KCTD12-induced desensitization results from a dual interaction with the G protein: constitutive binding stabilizes the heterotrimeric G protein at the receptor, whereas dynamic binding to the receptor-activated Gbetagamma subunits induces desensitization by uncoupling Gbetagamma from the effector K(+) channel. While receptor-free KCTD12 desensitizes K(+) currents activated by other GPCRs in vitro, native KCTD12 is exclusively associated with GABAB receptors. Accordingly, genetic ablation of KCTD12 specifically alters GABAB responses in the brain. Our results show that GABAB receptors are endowed with fast and reversible desensitization by harnessing KCTD12 that intercepts Gbetagamma signaling.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > Molecular Neurobiology Synaptic Plasticity (Bettler)
UniBasel Contributors:Bettler, Bernhard
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:17 Jul 2020 08:08
Deposited On:17 Jul 2020 08:05

Repository Staff Only: item control page