Initiation of Multidrug Transport at Fertilization.

描述(申请人提供)：成功的胚胎发育需要一系列细胞事件的协调执行，统称为发育程序，尽管细胞外环境不可预测。围绕受精的事件不仅启动了发育程序，还导致了细胞防御的获得，例如启动了由多药耐药相关转运体(MRP)介导的毒物/异体运输。受精时激活转运蛋白的机制尚不清楚，但似乎涉及转运蛋白囊泡的移位和它们插入质膜。这项建议的主要目的是，首先描述海胆卵中MRP转运蛋白转运体小泡的特征，其次描述它们在受精后向质膜的转运。该项目的结果将对受精时胚胎表面的重组以及MRP转运体在发育中的作用提供深入的见解。理解受精后MRP囊泡运输事件直接关系到更大的问题，即各种蛋白质的移位如何响应细胞外刺激，用于调节细胞和发育生理。

DESCRIPTION (provided by applicant): Successful embryonic development requires the coordinated execution of a cascade of cellular events, collectively referred to as the developmental program, despite an unpredictable extracellular environment. The events surrounding fertilization not only initiate the developmental program, but also result in the acquisition of cellular defenses such as the initiation of toxicant/xenobiotic transport mediated by multidrug resistance-associated (mrp) transporters. The mechanism responsible for activation of transport at fertilization is unknown but appears to involve translocation of transporter vesicles and their insertion into the plasma membrane. The main aims of this proposal are, first, to characterize mrp transporter vesicles in the sea urchin egg and second, to describe their translocation to the plasma membrane following fertilization. The results of this project will provide insights into the reorganization of embryonic surfaces at fertilization and the role of mrp transporters in development. Understanding mrp vesicle trafficking events following fertilization is directly related to the larger problem of how translocation of various proteins, in response to extracellular stimuli, is employed in regulation of cellular and developmental physiology.