D2 dopamine receptor activation of potassium channels is selectively decoupled by Galpha-specific GoLoco motif peptides.
D2 dopamine receptor activation of potassium channels is selectively decoupled by Galpha-specific GoLoco motif peptides.
复制标题
D2 多巴胺受体对钾通道的激活可通过 Galpha 特异性 GoLoco 基序肽选择性解耦。
DOI：
10.1111/j.1471-4159.2004.02997.x
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Oxford,GerryS
中科院分区：
文献类型：
--
作者：
Webb,ChristinaK;McCudden,ChristopherR;Willard,FrancisS;Kimple,RandallJ;Siderovski,DavidP;Oxford,GerryS
The GoLoco motif is a short polypeptide sequence found in G‐protein signaling regulators such as regulator of G‐protein signaling proteins type 12 and 14 and activator of G‐protein signaling protein type 3. A unique property of the GoLoco motifs from these three proteins is their preferential interaction with guanosine diphosphate (GDP)‐bound Gαi1, Gαi3and, sometimes, Gαi2subunits over Gαosubunits. This interaction prevents both spontaneous guanine nucleotide release and reassociation of Gαi‐GDP with Gβγ. We utilized this property of the GoLoco motif to examine dopamine (D2 and D3) and somatostatin receptor coupling to G‐protein‐regulated inwardly rectifying potassium (GIRK) channels in mouse AtT20 cells. GoLoco motif peptides had no effect on either basal channel activity or the initial responses to agonists, suggesting that the GoLoco motif cannot disrupt pre‐formed G‐protein heterotrimers. GoLoco motif peptides did, however, interfere with human D2(short)receptor coupling to GIRK channels as demonstrated by the progressively diminished responses after repeated agonist application. This behavior is consistent with some form of compartmentalization of D2 receptors and GIRK channels such that Gβγ subunits, freed by local receptor activation and prevented from reforming a heterotrimeric complex, are not functionally constrained within the receptor–channel complex and thus are unable to exert a persistent activating effect. In contrast, GoLoco motif peptides had no effect on either D3 or somatostatin coupling to GIRK channels. Our results suggest that GoLoco motif‐based peptides will be useful tools in examining the specificity of G‐protein‐coupled receptor–effector coupling.
