Auxiliary GABA(B) Receptor Subunits Uncouple G Protein beta gamma Subunits from Effector Channels to Induce Desensitization

0430025 - ÚEM 2015 RIV US eng J - Článek v odborném periodiku
Tureček, Rostislav - Schwenk, J. - Fritzius, T. - Ivankova, K. - Zolles, G. - Adelfinger, L. - Jacquier, V. - Besseyrias, V. - Gassmann, M. - Schulte, U. - Fakler, B. - Bettler, B.
Auxiliary GABA(B) Receptor Subunits Uncouple G Protein beta gamma Subunits from Effector Channels to Induce Desensitization.
Neuron. Roč. 82, č. 5 (2014), s. 1032-1044. ISSN 0896-6273. E-ISSN 1097-4199
Institucionální podpora: RVO:68378041
Klíčová slova: GABA(B) * animals * brain
Kód oboru RIV: FH - Neurologie, neurochirurgie, neurovědy
Impakt faktor: 15.054, rok: 2014

We studied mechanisms of KCTD12-induced desensitization of GABAB receptor activated K+ currents. Using proteomic and electrophysiological approaches, we now show that the desensitization results from a dual interaction of KCTD12 with the G protein: constitutive binding stabilizes the heterotrimeric G protein at the receptor, whereas dynamic binding to the receptor-activated Gbg subunits induces desensitization by uncoupling Gbg from the effector K+ channel. Our results show that GABAB receptors are endowed with fast and reversible desensitization by harnessing KCTD12 that intercepts Gbg signaling.
Trvalý link: http://hdl.handle.net/11104/0238724