Initiation of Multidrug Transport at Fertilization.

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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.