Reorganization of the Actin Cytoskeleton in Airway Smooth Muscle

气道平滑肌肌动蛋白细胞骨架的重组

基本信息

批准号：
8389615
负责人：
Dale D. Tang
金额：
$ 37.6万
依托单位：
ALBANY MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-12-01 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8389615
关键词：
Actins Adherens Junction Affect Agonist Asthma Attenuated Biochemical Biological Assay Cell Adhesion Cell physiology Cells Cytoskeleton Development Disease Endocytosis Environment Equilibrium Event Gene Expression Glia Maturation Factor Goals In Vitro Knowledge Life Light Mediating Microfilaments Microscopy Molecular Muscle Contraction Myopathy Myosin ATPase Peptides Physiological Pilot Projects Play Process Property Proteins RNA Interference Regulation Research Role Smooth Muscle Smooth Muscle Myocytes Striated Muscles Structure Subfamily lentivirinae System Technology Testing Time Tissues Transfection adapter protein airway hyperresponsiveness base cell assembly depolymerization effective therapy improved migration monomer new technology novel novel strategies polymerization prevent programs receptor respiratory smooth muscle response stem transmission process

项目摘要

DESCRIPTION (provided by applicant): In addition to myosin activation, the actin cytoskeleton undergoes reorganization in airway smooth muscle (a key regulator of airway tone) in response to contractile stimulation, which plays an essential role in the regulation of force development. The dynamic changes in the actin cytoskeleton may enable smooth muscle cells to adjust their structure and contractility in response to alterations in environments surrounding them. In contrast, the actin cytoskeleton of striated muscles is relatively stable. Myosin activation may serve as the "engine" for smooth muscle contraction whereas remodeling of the actin cytoskeleton including actin polymerization may function as the "transmission system" in smooth muscle. However, the cellular and molecular mechanisms that regulate the dynamic actin cytoskeleton are not well understood. Our pilot studies show that the actin-associated protein Abi is highly expressed in airway smooth muscle. In Aim 1, physiological role of Abi in the regulation of actin polymerization in airway smooth muscle will be characterized. In Aim 2, the physiological properties of the actin depolymerizer GMF in regulating actin depolymerization in airway smooth muscle will be evaluated. In Aim 3, the formation and/or assembly of adherens junctions in airway smooth muscle upon contractile stimulation will be assessed. To accomplish the goal, several novel approaches such as a new technology to manipulate gene expression in smooth muscle tissues, cell-permeable peptides, the sensitive biochemical assay, and confocal fluorescent microscopy will be utilized. Completion of these studies should define the novel roles and regulation of the actin cytoskeleton and adherens junctions in airway smooth muscle, which may establish a new paradigm for the regulation of smooth muscle contraction. Obtaining this knowledge is fundamental to develop new strategies for more effective treatment of airway diseases such as asthma.

描述（由申请人提供）：除了肌球蛋白激活外，肌动蛋白细胞骨架还会在气道平滑肌（气道张力的关键调节剂）中重组，以响应收缩性刺激，这在武力发育的调节中起着至关重要的作用。肌动蛋白细胞骨架的动态变化可能使平滑肌细胞能够根据周围环境的改变来调整其结构和收缩力。相反，横纹肌肉的肌动蛋白细胞骨架相对稳定。肌球蛋白激活可以用作平滑肌收缩的“发动机”，而包括肌动蛋白聚合（包括肌动蛋白聚合）的肌动蛋白细胞骨架的重塑可能是平滑肌中的“传输系统”。但是，调节动态肌动蛋白细胞骨架的细胞和分子机制尚不清楚。我们的试点研究表明，与肌动蛋白相关的蛋白ABI在气道平滑肌中高度表达。在AIM 1中，将表征ABI在气道平滑肌中肌动蛋白聚合调节中的生理作用。在AIM 2中，将评估肌动蛋白去聚合剂GMF在调节气道平滑肌中肌动蛋白去聚合中的生理特性。在AIM 3中，将评估在收缩刺激时气道平滑肌中粘附连接的形成和/或组装。为了实现目标，将利用几种新的方法，例如一种新技术来操纵基因表达，可渗透细胞可渗透的肽，灵敏的生化测定和共聚焦荧光显微镜。这些研究的完成应定义肌动蛋白细胞骨架和气道平滑肌的粘附连接的新作用和调节，这可能会为调节平滑肌收缩的新范式建立新的范式。获得此知识是制定新策略以更有效治疗气道疾病（例如哮喘）的基础。