MECHANISM OF ANGIOTENSIN II (AT1A) RECEPTOR ENDOCYTOSIS

细胞表面受体的内吞作用抑制细胞反应， 介导细胞再敏感化。内吞受体包含 在它们的细胞质结构域中的内化基序， 内吞机制和促进受体迁移， 在配体刺激下的内化。血管紧张素-II（AT 1A）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。 本提案的总体目标是检验氨基 酸残基以前被认为是重要的内化 AT 1A有助于与内吞作用相互作用的内化基序， 促进内部化的机制。 在AIM 1中，我们将充分 通过特异性突变氨基酸来表征这些基序 围绕着先前确定的重要残基。在AIM II中，我们 将构建含有非- AT 2和AT 1A片段的内化被认为是重要的 为了确定这些区域在AT 1A中的作用， 内吞作用最后，在AIM III中，我们将确定特定区域或 AT 1A羧基尾部的氨基酸与 内吞机制

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.