MEMBRANE TARGETING/FUSION DURING VESICULAR TRAFFIC

（摘自申请人摘要）：提出的研究目标 是为了进一步了解膜运输的机制。的 工作将集中在TAP（转胞吞作用相关蛋白 复合物，最近发现的融合所需的蛋白质复合物 特定的膜伴侣，但不是所有的融合事件所必需的。 该复合物特异性地与转胞吞载体囊泡结合 （TCV），并且是它们与顶端质膜融合所必需的 （下午）。这些数据表明，该复合物参与了膜 识别事件。目前，只有小的GTP结合蛋白是已知的 参与膜分选，并因此定义其他 影响这一过程的因素对于 阐明介导膜特异性的机制。 博士Sztul计划描述TAP复合物的亚基结构 并定义不同亚单位的功能。她将分析 功能TAP复合体组装的要求，并研究 其与TCV膜特异性附着的机制。她还将 分析复合物的形态，并将不同的功能 具有形态学定义结构的域。的功能 复合物将在改良的测定中进行评估，其中靶向和 结合可以与融合的后期阶段分开。使用该系统， TAP复合物与其他已知影响 将检查泡状交通。大多数功能分析将 利用生物化学和形态学方法， 不同组分的表征将使用分子和遗传学方法， 程序.

(Adapted from applicant's abstract): The goal of the research proposed is to further understanding of the mechanisms of membrane traffic. The work will concentrate on the TAP (transcytosis associated protein complex, a recently identified complex of proteins required for fusion of specific membrane partners, but not required for all fusion events. The complex is specifically associated with transcytotic carrier vesicles (TCVs) and is necessary for their fusion with the apical plasma membrane (PM). The data suggests that the complex is involved in membrane recognition events. Currently, only small GTP-binding proteins are known to participate in membrane sorting, and consequently, defining other components that influence this process is of great significance for the elucidation of the mechanisms mediating membrane specificity. Dr. Sztul plans to characterize the subunit structure of the TAP complex and to define the function of distinct subunits. She will analyze the requirements for assembly of functional TAP complex and study the mechanism of its specific attachment to the TCV membrane. She will also analyze the morphology of the complex and correlate distinct functional domains with morphologically defined structures. The function of the complex will be assessed in a modified assay in which targeting and binding can be separated from later stages of fusion. Using the system, interactions of the TAP complex with other molecules known to influence vesicular traffic will be examined. Most of the functional analyses will utilize biochemical and morphological approaches while the characterization of distinct components will use molecular and genetic procedures.