Multidrug Resistance-Like Genes and Auxin Transport

本项目旨在确定AtMDR1和其他由拟南芥中一组ABC转运蛋白基因编码的与动物多药耐药(MDR)蛋白同源的蛋白的功能。研究最多的是动物MDR蛋白，因为它们在肿瘤对化疗药物的耐药性中起到了作用。这项研究将调查这些蛋白质在植物中扮演的角色。遗传、生化和生理证据表明，至少有两个拟南芥MDR蛋白参与植物激素生长素的运输，因此对植物的生长发育至关重要。生长素运输抑制因子NPA与AtMDR1和AtPGP1蛋白紧密结合。缺乏这些蛋白的基因敲除突变体在生长素的极性运输方面存在严重缺陷。基因敲除突变体的表型与生长素分布异常是一致的。产生这两个基因的大量背景信息的研究活动将被重复，以达到MDR样亚群中一些以前从未研究过的基因。此外，生化研究将检验有关AtMDR1功能机制的假说。例如，它是生长素转运蛋白还是生长素转运蛋白的调节器？实验计划包括鉴定基因敲除表型，确定基因敲除突变对生长素分布的影响，以及AtMDR1基因在异源系统中表达后的生化研究。负责该项目的两个专业人员具有互补的专长领域，并将为博士后研究助理和研究生提供跨学科培训。从遗传学、生化和生理学上对这些有趣基因的剖析有望为植物生长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.