Mutual action by Gγ and Gβ for optimal activation of GIRK channels in a channel subunit-specific manner

被引:8
作者
Tabak, Galit [1 ,2 ]
Keren-Raifman, Tal [1 ,2 ]
Kahanovitch, Uri [1 ,2 ,3 ]
Dascal, Nathan [1 ,2 ]
机构
[1] Tel Aviv Univ, Sackler Sch Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel
[2] Tel Aviv Univ, Sackler Sch Med, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel
[3] Virginia Tech, Sch Neurosci, Blacksburg, VA 24061 USA
基金
以色列科学基金会;
关键词
RECTIFYING K+ CHANNEL; MUSCARINIC POTASSIUM CHANNEL; PHOSDUCIN-LIKE PROTEIN; XENOPUS OOCYTES; DIMER FORMATION; BASAL ACTIVITY; G-ALPHA; MEMBRANE; BINDING; MECHANISM;
D O I
10.1038/s41598-018-36833-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The tetrameric G protein-gated K+ channels (GIRKs) mediate inhibitory effects of neurotransmitters that activate G(i/o)-coupled receptors. GIRKs are activated by binding of the G beta gamma dimer, via contacts with G beta. G gamma underlies membrane targeting of G beta gamma, but has not been implicated in channel gating. We observed that, in Xenopus oocytes, expression of G gamma alone activated homotetrameric GIRK1* and heterotetrameric GIRK1/3 channels, without affecting the surface expression of GIRK or G beta. G gamma and G beta acted interdependently: the effect of G gamma required the presence of ambient G beta and was enhanced by low doses of coexpressed G beta, whereas excess of either G beta or G gamma imparted suboptimal activation, possibly by sequestering the other subunit "away" from the channel. The unique distal C-terminus of GIRK1, G1-dCT, was important but insufficient for G gamma action. Notably, GIRK2 and GIRK1/2 were not activated by G gamma. Our results suggest that G gamma regulates GIRK1* and GIRK1/3 channel's gating, aiding G beta to trigger the channel's opening. We hypothesize that G gamma helps to relax the inhibitory effect of a gating element ("lock") encompassed, in part, by the G1-dCT; GIRK2 acts to occlude the effect of G gamma, either by setting in motion the same mechanism as G gamma, or by triggering an opposing gating effect.
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页数:17
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