Intracellular trafficking of angiotensin II and its AT(1) and AT(2) receptors: Evidence for selective sorting of receptor and ligand
Intracellular trafficking of angiotensin II and its AT(1) and AT(2) receptors: Evidence for selective sorting of receptor and ligand
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DOI：
10.1210/me.11.9.1266
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发表时间：
1997-08-01
影响因子：
--
通讯作者：
Kobilka, BK
中科院分区：
文献类型：
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作者：
Hein, L;Meinel, L;Kobilka, BK
血管紧张素Ⅱ(Ang II)与AT(1)和AT(2)两种受体亚型结合。在许多情况下，Ang II刺激受体后，细胞内信号转导迅速减敏，细胞表面受体数量减少。本研究旨在用免疫荧光显微镜观察稳定表达这两种受体亚型的人胚胎肾293细胞中Ang II及其A(1a)和AT(2)受体的细胞转运途径。AT(2)受体定位于质膜，在激动剂刺激下不发生内吞作用，去掉激动剂后，AT(1a)受体循环至质膜，而荧光标记的Ang II定位于溶酶体途径，即使稳态配基结合没有检测到表面受体的进一步丢失，荧光素Ang II仍被持续内化，通过抗体喂养检测到受体在内体囊泡和质膜之间的循环，这些实验为Ang II及其AT(1a)受体作为受体配体和复合体的亚型特异性受体的分选和内化提供了证据。他们认为，受体进入内体是动态平衡的，受体循环到质膜，最终AT(1a)受体和Ang II的内化在脱敏机制减弱了Ca~(2+)和1，4，5-三磷酸肌醇信号后继续存在。
Angiotensin II (Ang II) binds to two different receptor subtypes, AT(1) and AT(2) receptors, In many cases, receptor stimulation by Ang II is followed by a rapid desensitization of the intracellular signal transduction and a decrease in cell surface receptor number, The present study was designed to examine by immunofluorescence microscopy the cellular trafficking pathways of Ang II and its A(1a) and AT(2) receptors in human embryonal kidney 293 cells stably expressing these receptor subtypes, Fluorescently labeled Ang II and AT(1a) receptors were rapidly internalized into endosomes. AT(2) receptors were localized in the plasma membrane and did not undergo endocytosis upon agonist stimulation, After removal of agonist, AT(1a) receptors recycled to the plasma membrane, whereas fluorescently labeled Ang II was targeted to the lysosomal pathway, Even though no further loss of surface receptor was measurable by ligand binding at steady state, fluorescein-Ang II was continuously internalized, and cycling of receptor between endosomal vesicles and the plasma membrane was detected by antibody feeding, These experiments provide evidence for subtype-specific receptor sorting and internalization of Ang II and its AT(1a) receptor as a receptor-ligand complex, and they suggest that the sequestration of receptors into endosomes is in dynamic equilibrium with receptor cycling to the plasma membrane, Finally, internalization of AT(1a) receptors and Ang II persists after desensitization mechanisms have attenuated Ca2+ and inositol 1,4,5-trisphosphate signaling.