MECHANISM OF ANGIOTENSIN II (AT1A) RECEPTOR ENDOCYTOSIS

细胞表面受体的内吞作用抑制细胞反应和 介导细胞的再敏化。内吞细胞受体包含 与之相互作用的细胞质结构域中的内化基序 内吞机制和促进受体迁移和 配体刺激时的内化。血管紧张素-II(AT1A)G- 蛋白偶联受体含有两个胞质尾区， 有助于配体刺激的内吞作用。 这项提议的总体目标是检验氨基转移的假设 以前被认为对内化很重要的酸残基 AT1a有助于内化基序与内胞相互作用 促进内部化的机制。在目标1中，我们将充分 通过特定突变的氨基酸来表征这些基序 围绕着之前发现的重要残基。在Aim Il，我们 将构建嵌合受体，该受体包含非 内化AT2和AT1a片段被认为对 内化以确定这些区域在AT1a中的作用 内吞作用。最后，在AIM III中，我们将确定特定区域或 AT1a羧基尾部的氨基酸，与 内吞机械。

Endocytosis of cell surface receptors dampens cell responses and mediates cellular resensitization. Endocytosing receptors contain internalization motifs in their cytoplasmic domains which interact with the endocytic machinery and facilitate receptor migration and internalization upon ligand stimulation. The angiotensin-II (AT1A) G- Protein coupled receptor contains two cytoplasmic tail regions which contribute to ligand-stimulated endocytosis. The overall goal of this proposal is to test the hypothesis that amino acid residues previously identified as important for internalization of AT1A contribute to internalization motifs which interact with endocytic machinery to facilitate internalization. In AIM 1, we will fully characterize these motifs by specifically mutating amino acids surrounding the previously identified important residues. In AIM Il, we will construct chimeric receptors containing regions of the non- internalizing AT2 and segments of AT1A deemed to be important for internalization in order to determine the role of these regions in AT1A endocytosis. Finally, in AIM III, we will determine specific regions or amino acids of the AT1A carboxyl tail which interact with the endocytotic machinery.