Copper entry into human cells

铜是一种必需的营养素，是许多不同的细胞过程所需要的。它在抗氧化防御、神经递质生物合成和其他一些重要的生化转化中是重要的辅助因子。虽然低水平的细胞对人体健康至关重要，但高水平是有毒的。因此，铜从细胞和组织的进入和消除是非常重要的途径。最近，一种负责调节铜进入人体细胞的蛋白质被确定为hCtr1。这个完整的膜蛋白由190个氨基酸残基组成，并且看起来（从亲水分析），像它的酵母同源物一样跨越膜三次。它已被证明是正常胚胎发育所必需的。这个应用程序的PI最近

Copper is an essential nutrient and is required by a number of distinct cellular processes. It is important as a co-factor in anti-oxidant defense, in neurotransmitter biosynthesis and a number of other important biochemical transformations. Although the presence of low cellular levels is essential for human health, elevated levels are toxic. Thus, copper entry and elimination from cells and tissues are highly important pathways. Recently the protein responsible for mediating the entry of copper into human cells has been identified and is called hCtr1. This integral membrane protein consists of 190 arninoacid residues and appears (from hydropathy analysis), like its yeast homologues to span the membrane three times. It has been demonstrated to be essential for normal embryonic develpment. The PI of this application has recently achieved the successful heterologous expression of hCtr1 in insect cells infected with baculovirus particles containing the eDNA for hCtr1. The present application aims to provide the first detailed characterization of structure-function relations in hCtr1 and will investigate the mechanism of copper transport mediated by hCtr1. The studies will combine functional assays of isotopic copper uptake with mutagenic analysis of novel hCtr1 molecules. These studies will be augmented by an examination of trafficking of endogenous levels of hCtr1 in mammalian cells using confocal microscopy and specific Ab's produced by the PI's laboratory. The results of these studies will provide an essential starting point for an understanding of an important aspect of copper regulation in humans. Disruptions in copper metabolism and homeostasis have been associated with several neurodegenerative conditions and the development of new therapeutic strategies requires greater knowledge of the regulatory pathways in normal and diseased states.