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The role of actin isoforms and posttranslational modifications for cytoskeletal dynamics in the amoeba Dictyostelium discoideum

肌动蛋白亚型和翻译后修饰对阿米巴盘基网柄菌细胞骨架动力学的作用

基本信息

批准号：
120503880
负责人：
Professor Dr. Michael Schleicher
金额：
--
依托单位：
Institut für Zellbiologie (aufgelöst)
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2009
资助国家：
德国
起止时间：
2008-12-31 至 2013-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/120503880?language=en
关键词：
role actin isoforms posttranslational modifications

项目摘要

Conventional actin is a highly conserved protein in all eukaryotes and well understood as the backbone of the microfilamentous system. However, very little is known about actin isoforms which do not belong to the tissue specific conventional ,, actin species. Do they copolymerize, form highly specific filaments, cap or crosslink or sever conventional actin filaments, are they subunits of larger protein complexes, are actin isoforms posttranslationally modified and thus regulated in structure and function? This proposal aims (a) at understanding of an entire actin system, and (b) at arginylation as an important posttranslational modification for cytoskeletal activities. The amoeba Dictyostelium discoideum is an ideal model system for these studies because the whole set of actin isoforms is known, and the system is amenable for sophisticated techniques of cell biology, molecular genetics, protein expression, and protein biochemistry. Identification of the individual actin isoforms, their expression patterns, arginylation and subcellular distribution will be important experimental approaches. In parallel, molecular genetics, expression of distinct constructs and biochemistry on the expressed actins and hybrids will then tell us how actin isoforms and their modifications help to orchestrate a complex cytoskeletal system.

传统肌动蛋白是所有真核生物中高度保守的蛋白质，并且被认为是微丝系统的骨架。然而，对于不属于组织特异性的常规肌动蛋白种类的肌动蛋白亚型知之甚少。它们是否共聚，形成高度特异性的细丝，帽或交联或切断传统的肌动蛋白细丝，它们是否是更大蛋白复合物的亚基，肌动蛋白亚型是否经过后期修饰，从而在结构和功能上受到调节？这个建议的目的是（a）在理解一个完整的肌动蛋白系统，（B）在β-羟化作为一个重要的翻译后修饰的细胞骨架活动。盘状网柄阿米巴是这些研究的理想模型系统，因为整套肌动蛋白亚型是已知的，并且该系统适合于细胞生物学、分子遗传学、蛋白质表达和蛋白质生物化学的复杂技术。鉴定单个肌动蛋白异构体，它们的表达模式，乙酰化和亚细胞分布将是重要的实验方法。与此同时，分子遗传学、不同结构的表达以及肌动蛋白和杂交体的生物化学将告诉我们肌动蛋白亚型及其修饰如何帮助协调复杂的细胞骨架系统。