Multidrug Resistance-Like Genes and Auxin Transport

本项目旨在研究拟南芥中一组ABC转运蛋白基因编码的AtMDR 1等与动物多药耐药（MDR）蛋白同源的蛋白的功能。 动物MDR蛋白最常被研究的是它们在癌症肿瘤对化疗药物的抗性中的作用。这项研究将调查这些蛋白质在植物中发挥的作用。 遗传学、生物化学和生理学证据表明，至少有两种拟南芥MDR蛋白参与植物激素生长素的运输，因此对植物生长和发育很重要。 生长素转运抑制剂NPA与AtMDR 1和AtPGP 1蛋白紧密结合。 缺少这些蛋白质的敲除突变体在极性生长素运输中具有严重缺陷。 基因敲除突变体的表型与生长素分布异常是一致的。 研究活动，产生了大量的背景信息，这两个基因将被重申，以达到一些以前从未研究过的基因内的MDR-样亚群。 此外，生化研究将测试关于AtMDR 1功能机制的假设。 例如，它是生长素转运蛋白还是生长素转运蛋白的调节子？ 实验计划包括表征敲除表型，确定生长素分布的敲除突变的影响，和AtMDR 1基因在异源系统中表达后的生化研究。 负责该项目的两个PI具有互补的专业领域，并将为博士后研究助理和研究生提供跨学科培训。 这些有趣的基因在遗传学、生物化学和生理学上的解剖有望为植物生长和发育的激素控制提供新的见解。

This project is designed to determine the functions of AtMDR1 and other proteins encoded by a group of ABC transporter genes in Arabidopsis that are homologous to multi-drug resistance (MDR) proteins of animals. The animal MDR proteins are most often studied for their roles in the resistance of cancer tumors to chemotherapeutic drugs. This research will investigate the roles these proteins play in plants. Genetic, biochemical, and physiological evidence indicates that at least two of the Arabidopsis MDR proteins participate in the transport of the plant hormone auxin, and thus are important to plant growth and development. The auxin-transport inhibitor NPA binds tightly to AtMDR1 and AtPGP1 proteins. Knockout mutants lacking these proteins have severe defects in polar auxin transport. The phenotypes of the knockout mutants are consistent with abnormal auxin distribution being the cause. The research activities that produced the substantial background information on these two genes will be reiterated to reach some never-before studied genes within the MDR-like subcluster. In addition, biochemical studies will test hypotheses about the mechanism of AtMDR1 function. For example, is it an auxin transporter or a regulator of an auxin transporter? The experimental plan includes characterizing knockout phenotypes, determining the effects of the knockout mutations on auxin distribution, and biochemical studies of the AtMDR1 gene after expression in a heterologous system. The two PIs responsible for the project have complementary areas of expertise and will provide interdisciplinary training for postdoctoral research associates and graduate students. The dissection of these interesting genes genetically, biochemically, and physiologically is expected to provide new insight into the hormonal control of plant growth and development.