Red Cell Cytoskeletal Protein 4. 1 During Cell Division

细胞分裂期间的红细胞细胞骨架蛋白 4. 1

• 批准号: 7094641
• 负责人: SHARON W KRAUSS
• 金额: $ 26.46万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7094641
• 关键词: RNA interference; actin binding protein; actins; cell cycle; cell free system; centrosome; chromatin; cytogenetics; cytoskeletal proteins; dynein ATPase; gene induction /repression; mass spectrometry; microtubules; molecular /cellular imaging; molecular assembly /self assembly; nuclear matrix; nuclear proteins; protein 4.1; protein isoforms; protein protein interaction; protein structure function; spindle pole body; subcellular fractionation; tissue /cell culture; western blottings

Multifunctional structural proteins, serving as linkers or adaptors, are essential for cellular remodeling processes. The long-term objective of this proposal is to elucidate how molecular interactions of structural proteins, particularly cytoskeletal protein 4.1, contribute to cell division. Protein 4.1 is a multifunctional structural protein that in red cells integrates components crucial for regulation of red cell skeletal organization and mechanical stability. However, it is now established that protein 4.1 is expressed in non-erythroid nucleated cells as well as in erythroid cells and is detected at sites such as centrosomes, mitotic spindles and nuclei. Although the role of protein 4.1 in mature red cells is well defined, its role(s) in nucleated cells are not well understood. We reported that 4.1 is required for microtubule organization and dynamics essential for proper mitotic spindle and centrosome formation. We also showed that at least two 4.1 domains directly function in assembly of these subcellular organelles. Our central hypothesis is that protein 4.1 interactions link or integrate structural components within centrosomes and spindle poles to provide dynamic properties necessary for assembly/disassembly during cell division. To obtain a detailed understanding of the interactions and mechanisms involved, two Aims are proposed: (1) elucidate mechanisms for 4.1 regulation of microtubule dynamics and organization in mitotic spindle poles and centrosomes, (2) determine how 4.1 expression affects cell division. We anticipate that identifying functional interactions of protein 4.1 will further increase our understanding of fundamental principles of assembly and dynamics of centrosomes and mitotic spindles during cell division and differentiation. This in turn may indicate the genesis of previously unrecognized pathological consequences of 4.1 gene defects. However, our investigations will also contribute a broad perspective on molecular disease loci involving defective or deficient cytoskeletal proteins.

多功能结构蛋白（用作接头或适配器）对于细胞重塑过程至关重要。该建议的长期目标是阐明结构蛋白（尤其是细胞骨架蛋白4.1）的分子相互作用如何有助于细胞分裂。蛋白质4.1是一种多功能结构蛋白，在红细胞中积分的组件对于调节红细胞骨骼组织和机械稳定性至关重要。然而，现在已经确定蛋白质4.1在非果蝇成核细胞以及红细胞细胞中表达，并在中心体，有丝分裂纺锤体和细胞核等位点检测到。尽管蛋白质4.1在成熟的红细胞中的作用得到了很好的定义，但其在成核细胞中的作用尚不清楚。我们报告说，微管组织需要4.1，而动力学对于适当的有丝分裂纺锤体和中心体形成必不可少。我们还表明，至少两个4.1域直接在这些亚细胞细胞器的组装中起作用。我们的中心假设是蛋白质4.1相互作用连接或整合了中心体内的结构成分，并在细胞分裂过程中提供了组装/拆卸所需的动态特性。为了获得对所涉及的相互作用和机制的详细了解，提出了两个目的：（1）阐明4.1调节微裂螺旋杆和中心体中微管动力学和组织的机制，（2）确定4.1表达如何影响细胞分裂。我们预计，鉴定蛋白质4.1的功能相互作用将进一步提高我们对细胞分裂和分化过程中的集装和丝质纺锤体动态的基本原理的理解。反过来，这可能表明了4.1基因缺陷的先前未被认可的病理后果的起源。但是，我们的研究还将对涉及缺陷或缺乏细胞骨架蛋白的分子疾病基因座有了广泛的看法。