KCTD Hetero-oligomers Confer Unique Kinetic Properties on Hippocampal GABA(B) Receptor-Induced K+ Currents

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F17%3A00478356" target="_blank" >RIV/68378041:_____/17:00478356 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1523/JNEUROSCI.2181-16.2016" target="_blank" >http://dx.doi.org/10.1523/JNEUROSCI.2181-16.2016</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1523/JNEUROSCI.2181-16.2016" target="_blank" >10.1523/JNEUROSCI.2181-16.2016</a>

Result language

angličtina

Original language name

KCTD Hetero-oligomers Confer Unique Kinetic Properties on Hippocampal GABA(B) Receptor-Induced K+ Currents

Original language description

GABA(B) receptors are the G-protein coupled receptors for the main inhibitory neurotransmitter in the brain, GABA. GABAB receptors were shown to associate with homo-oligomers of auxiliary KCTD8, KCTD12, KCTD12b, and KCTD16 subunits (named after their T1 K+-channel tetramerization domain) that regulate G-protein signaling of the receptor. Here we provide evidence that GABAB receptors also associate with hetero-oligomers of KCTD subunits. Coimmunoprecipitation experiments indicate that two-thirds of the KCTD16 proteins in the hippocampus of adult mice associate with KCTD12. We show that the KCTD proteins hetero-oligomerize through self-interacting T1 and H1 homology domains. Bioluminescence resonance energy transfer measurements in live cells reveal that KCTD12/KCTD16 hetero-oligomers associate with both the receptor and the G-protein. Electrophysiological experiments demonstrate that KCTD12/KCTD16 hetero-oligomers impart unique kinetic properties on G-protein-activated Kir3 currents. During prolonged receptor activation (one min) KCTD12/KCTD16 hetero-oligomers produce moderately desensitizing fast deactivating K+ currents, whereas KCTD12 and KCTD16 homo-oligomers produce strongly desensitizing fast deactivating currents and nondesensitizing slowly deactivating currents, respectively. During short activation (2 s) KCTD12/KCTD16 hetero-oligomers produce nondesensitizing slowly deactivating currents. Electrophysiological recordings from hippocampal neurons of KCTD knock-out mice are consistent with these findings and indicate that KCTD12/KCTD16 hetero-oligomers increase the duration of slow IPSCs. In summary, our data demonstrate that simultaneous assembly of distinct KCTDs at the receptor increases the molecular and functional repertoire of native GABAB receptors and modulates physiologically induced K+ current responses in the hippocampus.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10602 - Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology

Project

<a href="/en/project/GA14-28334S" target="_blank" >GA14-28334S: Molecular mechanism of GABA B receptor regulation by KCTD proteins</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Neuroscience

ISSN

0270-6474

e-ISSN

—

Volume of the periodical

37

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

1162-1175

UT code for WoS article

000393570700010

EID of the result in the Scopus database

2-s2.0-85011333626