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CELLULAR FUNCTION OF ACTIN HOMOLOGUES

肌动蛋白同系物的细胞功能

基本信息

批准号：
2459488
负责人：
DAVID I MEYER
金额：
$ 17.57万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-08-01 至 1999-07-31
项目状态：
已结题

项目摘要

Centractins represent a family of highly-conserved mammalian genes whose sequences indicate a significant degree of similarity (>70%) to actin. Members of this family have been localized to centrosomes and large vesicular structures by morphological analyses. In addition, biochemical studies have shown that centractins are associated with a 20S cytosolic proteinaceous particle known as the p150(Glued), or dynactin complex. This complex has been implicated in the function of cytoplasmic dynein, a molecular motor which is responsible for retrograde vesicular transport along microtubules. As at least two isoforms of centractin have been characterized in our laboratory, as well as a novel yeast actin-related protein (ARP) which may represent a functional homologue of centractin. It is the aim of the research described here to use biochemical, morphological and genetic techniques to answer the most fundamental questions pertinent to the role of centractins in cellular function. These include: As centractin isoforms have individual subcellular localizations, how do they differ functionally? Are centractins capable of polymerizing into multimeric complexes or filaments, in a fashion homologous to actin, or to serve as actin-binding proteins? What is the "centractin phenotype" in mammalian cells whose centractin expression or integrity has been compromised? Is the yeast ARP, ACT3, the functional homologue of centractin, and if so what is its role in this organism?

centractin代表一个高度保守的哺乳动物基因家族，序列表明与肌动蛋白具有显著程度的相似性（>70%）。该家族的成员已定位于中心体和大泡状结构的形态学分析。此外，生物化学研究表明，centractin与20S胞质称为p150（胶合）或动力蛋白复合物的蛋白质颗粒。这复合物与细胞质动力蛋白的功能有关，负责囊泡逆行转运的分子马达沿着微管。由于至少两种centractin的同种型已经被发现，在我们的实验室，以及一个新的酵母肌动蛋白相关的特点，蛋白质（阿普），其可能代表centractin的功能同源物。这里描述的研究的目的是使用生物化学，形态学和遗传学技术来回答最基本的与centractin在细胞功能中的作用有关的问题。这些包括：由于centractin同种型具有单独的亚细胞定位，它们在功能上有什么不同？centractin是否能够聚合以与肌动蛋白同源的方式，还是作为肌动蛋白结合蛋白什么是“centractin表型” 在centractin表达或完整性已经被破坏的哺乳动物细胞中，妥协了吗是酵母阿普，ACT 3， centractin，如果是这样，它在这种生物体中的作用是什么？