Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
Proc Natl Acad Sci U S A 2002 Aug 06;9916:10783-8. doi: 10.1073/pnas.162346199.
Show Gene links Show Anatomy links

Graded contribution of the Gbeta gamma binding domains to GIRK channel activation.

Sadja R , Alagem N , Reuveny E .

G protein coupled inwardly rectifying K(+) channels (GIRK/Kir3.x) are mainly activated by a direct interaction with Gbetagamma subunits, released upon the activation of inhibitory neurotransmitter receptors. Although Gbetagamma binding domains on all four subunits have been found, the relative contribution of each of these binding sites to channel gating has not yet been defined. It is also not known whether GIRK channels open once all Gbetagamma sites are occupied, or whether gating is a graded process. We used a tandem tetrameric approach to enable the selective elimination of specific Gbetagamma binding domains in the tetrameric context. Here, we show that tandem tetramers are fully operational. Tetramers with only one wild-type channel subunit showed receptor-independent high constitutive activity. The presence of two or three wild-type subunits reconstituted receptor activation gradually. Furthermore, a tetramer with no GIRK1 Gbetagamma binding domain displayed slower kinetics of activation. The slowdown in activation was found to be independent of regulator of G protein signaling or receptor coupling, but this slowdown could be reversed once only one Gbetagamma binding domain of GIRK1 was added. These results suggest that partial activation can occur under low Gbetagamma occupancy and that full activation can be accomplished by the interaction with three Gbetagamma binding subunits.

PubMed ID: 12124401
PMC ID: PMC125044
Article link: Proc Natl Acad Sci U S A

Species referenced: Xenopus
Genes referenced: kcnj3 suclg2

References [+] :
Breitwieser, Mechanism of muscarinic receptor-induced K+ channel activation as revealed by hydrolysis-resistant GTP analogues. 1988, Pubmed