Preassembly of specific Gβγ subunits at GABAB receptors through auxiliary KCTD proteins accelerates channel gating
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F24%3A00598840" target="_blank" >RIV/68378041:_____/24:00598840 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S000629522400159X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S000629522400159X?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bcp.2024.116176" target="_blank" >10.1016/j.bcp.2024.116176</a>
Alternative languages
Result language
angličtina
Original language name
Preassembly of specific Gβγ subunits at GABAB receptors through auxiliary KCTD proteins accelerates channel gating
Original language description
GABAB receptors (GBRs) are G protein-coupled receptors for GABA, the main inhibitory neurotransmitter in the brain. GBRs regulate fast synaptic transmission by gating Ca2+ and K+ channels via the Gβγ subunits of the activated G protein. It has been demonstrated that auxiliary GBR subunits, the KCTD proteins, shorten onset and rise time and increase desensitization of receptor-induced K+ currents. KCTD proteins increase desensitization of K+ currents by scavenging Gβγ from the channel, yet the mechanism responsible for the rapid activation of K+ currents has remained elusive. In this study, we demonstrate that KCTD proteins preassemble Gβγ at GBRs. The preassembly obviates the need for diffusion-limited G protein recruitment to the receptor, thereby accelerating G protein activation and, as a result, K+ channel activation. Preassembly of Gβγ at the receptor relies on the interaction of KCTD proteins with a loop protruding from the seven-bladed propeller of Gβ subunits. The binding site is shared between Gβ1 and Gβ2, limiting the interaction of KCTD proteins to these particular Gβ isoforms. Substituting residues in the KCTD binding site of Gβ1 with those from Gβ3 hinders the preassembly of Gβγ with GBRs, delays onset and prolongs rise time of receptor-activated K+ currents. The KCTD-Gβ interface, therefore, represents a target for pharmacological modulation of channel gating by GBRs.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GA21-17085S" target="_blank" >GA21-17085S: The role of GABAB receptor-associated KCTD16 proteins in the sensory nervous system</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biochemical Pharmacology
ISSN
0006-2952
e-ISSN
1873-2968
Volume of the periodical
228
Issue of the periodical within the volume
October
Country of publishing house
GB - UNITED KINGDOM
Number of pages
17
Pages from-to
116176
UT code for WoS article
001317337900001
EID of the result in the Scopus database
2-s2.0-85189674846