Erythroid Iron Transport

红细胞铁转运

• 批准号: 7636978
• 负责人: NANCY CATHERINE ANDREWS
• 金额: $ 5.42万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7636978
• 关键词: Abbreviations; Accounting; Acute Erythroblastic Leukemia; Affect; Anemia; Assimilations; BAC (bacterial artificial chromosome); Biology; Candidate Disease Gene; Cell Line; Cellular biology; Child; Chromosomes; Chromosomes, Human, Pair 19; Code; Complement; Cytochromes b; Defect; Development; Dimethyl Sulfoxide; Disease; Early Endosome; Endosomes; Endowment; Equilibrium; Erythrocytes; Erythroid; Erythroid Progenitor Cells; Erythropoiesis; Finding of Mean Corpuscular Hemoglobin; Funding; Genes; Goals; Hematocrit procedure; Hemoglobin; Homeodomain Proteins; Homeostasis; Homologous Gene; Individual; Insulinase; Iron; Iron Metabolism Disorders; MEL Gene; Maps; Molecular; Mus; Mutant Strains Mice; Mutation; Nature; Oxygen; Pattern; Phenotype; Play; Process; Proline; Proteins; Rab8 protein; Rate; Reticulocytes; Role; SLC11A2 gene; Transferrin; Transferrin Receptor; Transgenic Organisms; Woman; Work; Yeasts; embryonic stem cell; holotransferrin; human morbidity; iron (III) reductase; iron metabolism; kinesin-like protein 1; mean corpuscular volume observed; mortality; mutant; receptor mediated endocytosis; research study; uptake

DESCRIPTION (provided by applicant): Disorders of iron metabolism are among the most prevalent causes of human morbidity and mortality. Iron deficiency affects up to 1 billion individuals worldwide, primarily women and children. The severe deficiency state presents with anemia, because most of the body's iron is used to make red blood cells, and normal red cell development depends on the availability of adequate amounts of iron. Red blood cells appropriate almost three quarters of the body's iron endowment to produce the oxygen-carrying protein hemoglobin. They require mechanisms to transport iron efficiently and to coordinate its acquisition with other aspects of differentiation. Erythroid iron is taken up through receptor-mediated endocytosis of iron-loaded transferrin (Tf), termed the Tf cycle. In the last funding period we showed that the Tf cycle plays a unique and essential role in normal erythropoiesis. In the experiments described here we will study hbd mice, a strain with a spontaneous mutation resulting in impaired erythroid iron assimilation, to better understand this process. We have mapped the hbd mutation to a small segment of mouse chromosome 19, which contains 4 possible candidate genes. The aims of the work described in this proposal are to characterize the biology of the hbd defect in mutant reticulocytes, to identify the molecular nature of the hbd defect, and to determine the role of the hbd gene product in erythropoiesis. This will be accomplished through detailed comparison of steps of the Tf cycle in hbd versus wild type reticulocytes, identification of all possible mutations within the hbd candidate region, transgenic rescue of the hbd phenotype, and determination of the subcellular localization and function of the hbd gene product. We anticipate that information derived from these experiments will be relevant to disorders of erythropoiesis and iron balance.

描述（由申请人提供）：铁代谢的疾病是人类发病率和死亡率最普遍的原因之一。铁缺乏症影响全球多达10亿个人，主要是妇女和儿童。严重的缺乏状态表现出贫血，因为大多数人的铁用于制造红细胞，而正常的红细胞发育取决于足够的铁。红细胞将几乎四分之三的铁赋予产生含氧蛋白质血红蛋白。他们需要有效地运输铁并与其他分化方面协调其获取的机制。红细胞铁通过受体介导的铁蛋白（TF）的内吞作用被称为TF循环。在最后的资金期间，我们表明TF周期在正常的红细胞生成中起着独特而重要的作用。在此处描述的实验中，我们将研究HBD小鼠，HBD小鼠是一种自发突变的菌株，导致红斑铁同化受损，以更好地理解这一过程。我们已将HBD突变映射到小鼠19的一小部分，其中包含4个可能的候选基因。本提案中描述的工作的目的是表征突变网状细胞中HBD缺陷的生物学，以鉴定HBD缺陷的分子特性，并确定HBD基因产物在促红细胞生成中的作用。这将通过详细比较HBD中TF周期与野生型网状细胞的详细比较，鉴定HBD候选区域内所有可能的突变，HBD表型的转基因营救以及确定HBD基因产品的亚细胞定位和功能。我们预计从这些实验中得出的信息将与红细胞生成和铁平衡的疾病有关。

项目成果

Scara5 is a ferritin receptor mediating non-transferrin iron delivery.

• DOI: 10.1016/j.devcel.2008.12.002
• 发表时间: 2009-01
• 期刊: DEVELOPMENTAL CELL
• 影响因子: 11.8
• 作者: Li, Jau Yi;Paragas, Neal;Ned, Renee M.;Qiu, Andong;Viltard, Melanie;Leete, Thomas;Drexler, Ian R.;Chen, Xia;Sanna-Cherchi, Simone;Mohammed, Farah;Williams, David;Lin, Chyuan Sheng;Schmidt-Ott, Kai M.;Andrews, Nancy C.;Barasch, Jonathan
• 通讯作者: Barasch, Jonathan