G protein-coupled receptor kinase function is essential for chemosensation in C-elegans
G protein-coupled receptor kinase function is essential for chemosensation in C-elegans
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DOI：
10.1016/s0896-6273(04)00252-1
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发表时间：
2004-05-27
期刊：
影响因子：
16.2
通讯作者：
Hart, AC
中科院分区：
文献类型：
--
作者：
Fukuto, HS;Ferkey, DM;Hart, AC
G蛋白偶联受体（GPCR）介导不同的信号传导过程，包括嗅觉。G蛋白偶联受体激酶（GRKs）是G蛋白信号转导的重要调节因子，特异性磷酸化激活的GPCR以终止信号转导。尽管先前描述了GRKs在GPCR信号下调中的作用，但缺乏C.线虫G蛋白偶联受体激酶-2（Ce-grk-2）功能对气味不敏感。相反，成年感觉神经元中Ce-grk-2功能的降低深刻地破坏了化学感觉，基于行为分析和Ca 2+成像。尽管哺乳动物arrestin蛋白与GRKs在受体脱敏中协同作用，但C. elegans arrestin-1（arrestin-1）不干扰化学感受。C.秀丽隐翅虫亚基odr-3或eat-16的缺失（其编码G蛋白信号传导（FIGS）蛋白的调节剂）恢复Ce-grk-2突变体中的化学感觉。这些结果表明，GRK功能的丧失可导致GPCR信号转导减少，并表明RGS蛋白在化学感受调节中的重要作用。
G protein-coupled receptors (GPCRs) mediate diverse signaling processes, including olfaction. G protein-coupled receptor kinases (GRKs) are important regulators of G protein signal transduction that specifically phosphorylate activated GPCRs to terminate signaling. Despite previously described roles for GRKs in GPCR signal downregulation, animals lacking C. elegans G protein-coupled receptor kinase-2 (Ce-grk-2) function are not hypersensitive to odorants. Instead, decreased Ce-grk-2 function in adult sensory neurons profoundly disrupts chemosensation, based on both behavioral analysis and Ca2+ imaging. Although mammalian arrestin proteins cooperate with GRKs in receptor desensitization, loss of C. elegans arrestin-1 (arr-1) does not disrupt chemosensation. Either overexpression of the C. elegans Galpha. subunit odr-3 or loss of eat-16, which encodes a regulator of G protein signaling (FIGS) protein, restores chemosensation in Ce-grk-2 mutants. These results demonstrate that loss of GRK function can lead to reduced GPCR signal transduction and suggest an important role for RGS proteins in the regulation of chemosensation.