Intracellular targeting and trafficking of thrombin receptors. A novel mechanism for resensitization of a G protein-coupled receptor.
Intracellular targeting and trafficking of thrombin receptors. A novel mechanism for resensitization of a G protein-coupled receptor.
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DOI：
10.1016/s0021-9258(18)47045-7
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发表时间：
1994-11
期刊：
影响因子：
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通讯作者：
Lutz Heinis;Kenji Ishiinit;Shaun R. Coughlinn;Brian;Kobilkai
中科院分区：
文献类型：
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作者：
Lutz Heinis;Kenji Ishiinit;Shaun R. Coughlinn;Brian;Kobilkai
凝血酶的蛋白水解酶受体是G蛋白偶联受体家族的成员，但由独特的蛋白分解机制激活。这种蛋白分解机制的不可逆性以及配体与其受体结合的事实引发了关于切割的受体失活和凝血酶反应性恢复的特殊问题。我们比较了在转基因的Rat1成纤维细胞中凝血酶受体和β2-肾上腺素能受体的细胞内转运。在未受刺激的细胞中，几乎所有的β2受体都位于质膜上；相比之下，部分细胞的凝血酶受体存在于与高尔基体标志共同定位的细胞膜上。激动剂的刺激引起β2肾上腺素能受体的内化和随后的循环，但大多数激活的凝血酶受体内化并靶向溶酶体。在未经刺激的细胞中发现的凝血酶受体池不受凝血酶的激活，但在细胞表面凝血酶受体激活时被转移到质膜上。质膜凝血酶受体的恢复与凝血酶反应性的恢复有关。这些观察揭示了一种新的运输机制，使凝血酶受体重新增敏，而不是其他G蛋白偶联受体的内化/再循环途径。
The receptor for the protease thrombin is a member of the G protein-coupled receptor family, but is activated by a unique proteolytic mechanism. The irreversibility of this proteolytic mechanism and the fact that the ligand is tethered to its receptor raise special questions about inactivation of cleaved receptors and recovery of thrombin responsiveness. We compared the intracellular trafficking of the thrombin receptor to that of the beta 2-adrenergic receptor in transfected Rat1 fibroblasts. In unstimulated cells almost all beta 2 receptors were located on the plasma membrane; by contrast, part of a cell's thrombin receptors were found in an intracellular membrane compartment which co-localized with Golgi markers. Stimulation by agonist caused internalization and subsequent recycling of the beta 2-adrenergic receptor, but most activated thrombin receptors were internalized and targeted to lysosomes. The intracellular pool of thrombin receptors found in unstimulated cells was protected from activation by thrombin, but was translocated to the plasma membrane upon activation of cell surface thrombin receptors. Replenishment of plasma membrane thrombin receptors correlated with recovery of thrombin responsiveness. These observations reveal a novel trafficking mechanism for resensitizing the thrombin receptor as opposed to the internalization/recycling pathway of other G protein-coupled receptors.