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Project Summary Regulation and sorting of leukocyte integrins are fundamental questions in cell adhesion and polarity that has great implication for various inflammatory and autoimmune diseases, but it has been poorly studied compared to cell adhesion receptors in fibroblast cells. We propose to investigate the sorting of leukocyte integrins and tetraspanin proteins that play critical role in immune cell adhesion and migration. We propose its dynamic sorting depends on a novel F-BAR-dependent mechanism that not only depends on curvature, but on a specific range of shallow curvature. We also propose that this mechanism is governing the mesoscale pattern these receptors are assembled, including propagating gradients and cortical oscillations, which link trafficking events to cell polarity. Specifically, in Aim 1, we plan to characterize surface expression and dynamics of these potential transmembrane protein cargos including integrin αMβ2 and CD81 after systematically identify and validate membrane cargos for the endocytic pathway mediated by F-BAR protein FBP17 and CIP4 using nonbiased proteomic approach. In Aim 2, we aim to isolate the factor of membrane curvature and tension using well-defined in vitro systems and to determine their effects on F- BAR membrane binding and tubulation. We will employ a nanobar-based supported bilayer system to critically evaluate if F-BAR protein senses curvature. We will also test the hypothesis that membrane tubulation may require lipid sorting and active membrane mechanics. These experiments will provide a quantitative biophysical understanding of how F-BAR proteins tubulate membranes without the hydrophobic insertion mechanisms commonly used by other BAR proteins. In Aim 3, we will dissect the functional consequences of the altered trafficking by examining spontaneous migration or migration under confinement. In particular, we will investigate the mechanism for polarized membrane receptor gradient formation. Collectively, combining advanced single cell imaging, genome-editing, proteomics, and in vitro reconstitution, the proposed research will shed key insights into the regulation and function of leukocyte integrins through sophisticated coordination and regulatory mechanisms operating at multiple spatial and temporal scales that have not yet been investigated.
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会议论文
Competition and Synergy of Arp2/3 and Formins in Nucleating Actin Waves.
Arp2/3 和 Formins 在成核肌动蛋白波中的竞争和协同作用。
DOI: 10.1101/2023.09.13.557508
发表时间: 2023
期刊: bioRxiv : the preprint server for biology
影响因子: --
作者: [LeChua,Xiang, Tong,CheeSan, Xǔ,XJ, Su,Maohan, Xiao,Shengping, Wu,Xudong, Wu,Min]
通讯作者: Wu,Min
Long noncoding RNAs interact with miRNAs to regulate inflammatory response
  • 批准号:
    9753931
  • 项目类别:
  • 资助金额:
    $34.75万
  • 财政年份:
    2018
  • 负责人:
    Min Wu
  • 依托单位:
Lung innate immunity against bacterial infection
  • 批准号:
    8762972
  • 项目类别:
  • 资助金额:
    $34.5万
  • 财政年份:
    2014
  • 负责人:
    Min Wu
  • 依托单位:
Lung innate immunity against bacterial infection
  • 批准号:
    8856487
  • 项目类别:
  • 资助金额:
    $34.5万
  • 财政年份:
    2014
  • 负责人:
    Min Wu
  • 依托单位:
Lung epithelium collaborates with alveolar macrophages in host defense
  • 批准号:
    8367586
  • 项目类别:
  • 资助金额:
    $41.4万
  • 财政年份:
    2012
  • 负责人:
    Min Wu
  • 依托单位:
国内基金
海外基金
Autoimmune diseases therapies: variations on the microbiome in rheumatoid arthritis