Regulation and function of transferrin receptor 2

转铁蛋白受体2的调节和功能

• 批准号: 6962220
• 负责人: CAROLINE ENNS
• 金额: $ 35.84万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6962220
• 关键词: clinical research; fluorescence microscopy; gene mutation; genetic regulation; hereditary hemochromatosis; human tissue; iron metabolism; liver cells; lysosomes; microarray technology; polymerase chain reaction; protein binding; protein protein interaction; protein purification; protein structure function; protein transport; proteomics; receptor expression; site directed mutagenesis; transferrin; transferrin receptor; western blottings; yeast two hybrid system

DESCRIPTION (provided by applicant): Hereditary hemochromatosis (HH) is the most common inherited disorder in people of Northern European descent. Iron overload damages organs leading to cirrhosis of the liver, diabetes, cardiomyopathy, and arthritis. Transferrin receptor 2 (TfR2) is a recently described protein with sequence similarity to the ubiquitous transferrin receptor (TfRl). The function of TfR2 is unknown. Mutated forms of TfR2 cause a form of hereditary hemochromatosis thus, implicating TfR2 as a key protein in the regulation of iron homeostasis in the body. TfR2 is found almost exclusively in hepatocytes. The liver is the major iron processing organ in the body, and iron sensing by this organ affects iron absorption by the intestines. Recent evidence shows that physiological concentrations of diferric transferrin (Tf) regulate TfR2 levels in hepatoma cell lines. Mouse models of iron overload support these findings. Since concentrations of diferric Tf generally reflect body iron levels in nonpathological conditions, TfR2 could signal iron levels by sensing diferric Tf. A model of how TfR2 senses Tf saturation and responds to regulate iron homeostasis in the body will be tested. The long term goal of this research is to understand how mutations in key proteins disturb the iron balance in the body and thereby reveal the mechanisms by which the body regulates iron homeostasis.

描述（由申请人提供）：遗传性血色素沉着症（HH）是北欧血统中最常见的遗传疾病。铁超载损害器官导致肝脏，糖尿病，心肌病和关节炎的肝硬化。转铁蛋白受体2（TFR2）是一种最近描述的蛋白质，与无处不在的转铁蛋白受体（TFRL）具有相似性。 TFR2的功能未知。 TFR2的突变形式引起了遗传性血色素沉着症的一种形式，这意味着TFR2是体内铁稳态调节的关键蛋白。 TFR2几乎完全在肝细胞中发现。肝脏是体内主要的铁加工器官，该器官的铁感应会影响肠的铁吸收。最近的证据表明，生理浓度的差异转铁蛋白（TF）调节肝癌细胞系中TFR2水平。铁超负荷的鼠标模型支持这些发现。由于差异TF的浓度通常反映在非人性条件下的人体铁水平，因此TFR2可以通过传感差异TF来信号铁水平。将测试TFR2如何感觉TF饱和度并响应调节体内铁稳态的模型。这项研究的长期目标是了解关键蛋白的突变如何干扰体内的铁平衡，从而揭示了人体调节铁稳态的机制。