Mechanosensing in LIM Domain Proteins

LIM 结构域蛋白中的机械传感

基本信息

批准号：
9259069
负责人：
Jonathan David Winkelman
金额：
$ 5.67万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-01 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9259069
关键词：
Actins Actomyosin Address Adherens Junction Apoptosis Atherosclerosis Binding Binding Sites Biochemical Biological Assay Biotin Cell Proliferation Cell division Cells Cellular biology Confocal Microscopy Cytoskeleton Decision Making Defect Detection Disease Distant Elements Environment Extracellular Matrix Family Family member Fiber Fibroblasts Focal Adhesions Heart failure Human In Vitro LIM Domain LIM Domain Protein Label Light Malignant Neoplasms Mass Spectrum Analysis Mechanical Stress Mechanics Microfilaments Modeling Molecular Monitor Myosin ATPase Myosin Type II Nature Pathway interactions Process Proteins Recruitment Activity Research Project Summaries Resolution Rupture Signal Pathway Site Specificity Streptavidin Stress Stress Fibers Stretching Structure System Testing Tissues Translating ZYX gene alpha Actinin blebbistatin cell behavior crosslink experience experimental study inhibitor/antagonist mechanical force mechanical load mechanical properties mechanotransduction member organ regeneration reconstitution repaired response sensor unnatural amino acids vasodilator-stimulated phosphoprotein

项目摘要

Project Summary: This research addresses a fundamental question in cell biology: How do cells detect mechanical stress in the actin cytoskeleton? The internal cytoskeletal tension is modulated by the mechanical properties of its external environment. Cytoskeletal tension can be an internal representation the mechanical properties of its local environment that can be “read” by the biochemical machinery. In fact proteins can be stretched by mechanical forces to reveal new binding sites, the recognition of these newly revealed binding sites by “sensor” proteins is one possible way of detecting mechanical information. The LIM superfamily represents a large number of putative mechanosensitive cellular proteins that detect stress by a completely unknown mechanism. I aim to identify the sequence determinants within the LIM domain responsible for detection of mechanical stress in the actin cytoskeleton. I then aim to discover the molecular mechanisms by which LIM domain proteins detect this stress, including identifying what LIM domains bind to and the nature of the deformation in the actin cytoskeleton. Revealing the mechanism of how a single member of this family detects cytoskeletal deformations will likely be generalizable to a large number of proteins. This will also drive future research involving how mechanosensitivity of each LIM protein is tuned and specificity achieved.

项目摘要：这项研究解决了细胞生物学中的一个基本问题：细胞如何检测肌动蛋白细胞骨架中的机械应力？内部细胞骨架张力受机械应力调节？细胞骨架张力可以是其外部环境的特性的内部表征。其局部环境的特性可以被生化机器“读取”。事实上，蛋白质可以是。通过机械力拉伸以揭示新的结合位点，识别这些新揭示的结合 “传感器”蛋白位点是检测 LIM 超家族的一种可能方法。代表大量推定的机械敏感细胞蛋白，它们通过完全检测压力我的目标是确定 LIM 结构域内负责的序列决定因素。然后，我的目标是通过检测肌动蛋白细胞骨架中的机械应力来发现分子机制。哪些 LIM 结构域蛋白可以检测到这种压力，包括识别 LIM 结构域所结合的内容以及其性质肌动蛋白细胞骨架的变形揭示了该家族的单个成员如何变形的机制。检测细胞骨架变形可能会推广到大量蛋白质，这也将推动。未来的研究涉及如何调整每种 LIM 蛋白的机械敏感性和实现特异性。