Lysophosphatidylcholine-induced surface redistribution regulates signaling of the murine G protein-coupled receptor G2A
Lysophosphatidylcholine-induced surface redistribution regulates signaling of the murine G protein-coupled receptor G2A
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DOI：
10.1091/mbc.e04-12-1044
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发表时间：
2005-05-01
影响因子：
3.3
通讯作者：
Witte, ON
中科院分区：
文献类型：
--
作者：
Wang, L;Radu, CG;Witte, ON
细胞内运输和膜受体的空间动力学关键调节受体功能。使用显微镜和亚细胞分级分析，我们研究了小鼠G蛋白偶联受体G2 A（muG 2A）的本地化。评价绿色荧光蛋白标记的、外源表达的以及内源性muG 2A，我们观察到该受体自发内化并积累在内体隔室中，而其表面表达通过溶血磷脂酰胆碱（LPC）处理增强并稳定。莫能菌素，一种循环途径的一般抑制剂，阻断LPC调节的muG 2A的表面定位以及muG 2A依赖性细胞外信号调节激酶（ERK）激活和LPC处理诱导的细胞迁移。保守的DRY基序（R-A）的突变增强了muG 2A的表面表达，导致其对莫能菌素抑制ERK活化的抗性。我们的数据表明，细胞内螯合和表面表达的LPC调节，而不是直接激动活性控制的信号转导反应的小鼠G2 A对LPC。
Intracellular trafficking and spatial dynamics of membrane receptors critically regulate receptor function. Using microscopic and subcellular fractionation analysis, we studied the localization of the murine G protein-coupled receptor G2A (muG2A). Evaluating green fluorescent protein-tagged, exogenously expressed as well as the endogenous muG2A, we observed that this receptor was spontaneously internalized and accumulated in endosomal compartments, whereas its surface expression was enhanced and stabilized by lysophosphatidylcholine (LPC) treatment. Monensin, a general inhibitor of recycling pathways, blocked LPC-regulated surface localization of muG2A as well as muG2A-dependent extracellular signal-regulated kinase (ERK) activation and cell migration induced by LPC treatment. Mutation of the conserved DRY motif (R-A) enhanced the surface expression of muG2A, resulting in its resistance to monensin inhibition of ERK activation. Our data suggest that intracellular sequestration and surface expression regulated by LPC, rather than direct agonistic activity control the signaling responses of murine G2A toward LPC.