Mechanism and Regulation of Actin-Based Retrograde Flow

基于肌动蛋白的逆行流的机制和调控

• 批准号: 6849606
• 负责人: JOHN H HENSON
• 金额: $ 19.92万
• 依托单位: DICKINSON COLLEGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6849606
• 关键词: actin binding protein; actins; biomechanics; calcium flux; cell morphology; cell motility; cell transformation; cyclic AMP; cytoskeleton; electron microscopy; extracellular matrix; guanine nucleotide binding protein; intermolecular interaction; intracellular transport; light microscopy; microfilaments; micromanipulator; microtubules; myosins; polymerization; protein localization; protein structure function; protein transport; sea urchins; transport proteins

DESCRIPTION (provided by applicant): Retrograde flow is a form of cell motility that is mediated by the actin cytoskeleton and is widespread in eukaryotic cells. The flow process involves the continual movement of the lamellipodial plasma membrane, membrane proteins and underlying actin cytoskeleton from the cell periphery towards the cell center. This phenomenon has been indicated as being important in cellular translocation, in the targeting of cellular migrations, in cell-substrate interactions, and in modulating the crosstalk between actin and microtubules. Retrograde flow has been extensively studied in only a few cell types (particularly neurons and mammalian and amphibian tissue culture cells) and, despite these efforts, the exact mechanism and regulation of this fundamental process is still largely unknown. The objective of this proposal is to expand the knowledge of the mechanisms underlying retrograde flow using a unique experimental model, the sea urchin coelomocyte. These cells display a highly exaggerated form of retrograde flow and possess a number of attributes which make them well suited for this study, including their optical properties, the availability of immunological probes for cytoskeletal proteins, and the readiness with which flow can be started and stopped and the cytoskeletal organization can be altered. Light and electron microscopic methods, combined with pharmacological and micromanipulation approaches will be used to address the following Specific Aims: 1. To determine the structural and functional relationships between actin filaments and actin-binding and motor proteins in the context of coelomocyte retrograde flow 2. To elucidate the physical forces operating in the context of coelomocyte retrograde flow. 3. To analyze the structural and functional relationships between actin filaments and microtubules in the context of coelomocyte retrograde flow. 4. To study the inducible transformation of coelomocytes from a lamellipodial to a filopodial form.

描述（由申请人提供）：逆行流是由肌动蛋白细胞骨架介导的细胞运动的一种形式，在真核细胞中广泛。流动过程涉及层状质膜，膜蛋白和基础肌动蛋白细胞骨架的持续运动，从细胞周围向细胞中心。该现象已被表明在细胞易位，细胞迁移，细胞基底相互作用以及调节肌动蛋白和微管之间的串扰中很重要。逆行流量仅在几种细胞类型（尤其是神经元，哺乳动物和两栖动物组织培养细胞）中进行了广泛的研究，尽管有这些努力，但这种基本过程的确切机制和调节仍然很大程度上是未知的。该提案的目的是使用独特的实验模型，海胆核细胞来扩展对逆行流量基础机制的知识。这些细胞表现出高度夸张的逆行流动形式，并具有许多属性，使它们非常适合本研究，包括其光学特性，细胞骨架蛋白的免疫学探针的可用性以及可以启动和停止流动的准备和细胞骨架组织的准备就绪。光和电子微观方法，结合药理和微观计量方法将用于解决以下特定目的： 1。确定肌动蛋白丝与肌动蛋白结合和运动蛋白之间的结构和功能关系。 2。为了阐明在岩体细胞逆行流动的背景下运行的物理力。 3。分析肌动蛋白丝和微管之间的结构和功能关系。 4。研究核细胞从薄膜片到丝状形式的诱导型转化。

项目成果

Echinoderm immunity.

• DOI: 10.1007/978-1-4419-8059-5_14
• 发表时间: 2010
• 期刊: Advances in experimental medicine and biology
• 作者: L. Smith;J. Ghosh;Katherine M. Buckley;Lori A. Clow;N. Dheilly;T. Haug;J. Henson;Chun Xing Li;C. Lun;A. Majeske;V. Matranga;S. Nair;J. Rast;D. Raftos;Mattias Roth;S. Sacchi;Catherine S. Schrankel;Klara Stensvåg

Broadening the spectrum of actin-based protrusive activity mediated by Arp2/3 complex-facilitated polymerization: motility of cytoplasmic ridges and tubular projections.

• DOI: 10.1002/cm.21186
• 发表时间: 2014-08
• 期刊: CYTOSKELETON
• 影响因子: 2.9
• 作者: Henson, John H.;Gianakas, Anastasia D.;Henson, Lauren H.;Lakin, Christina L.;Voss, Meagen K.;Bewersdorf, Joerg;Oldenbourg, Rudolf;Morris, Robert L.
• 通讯作者: Morris, Robert L.