Intermediate Filaments: Motility, Motors and Cytoskeletal Interactions

中间丝：运动性、马达和细胞骨架相互作用

• 批准号: 10227014
• 负责人: Vladimir I Gelfand
• 金额: $ 25.16万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227014
• 关键词: Acetylation; Actins; Adhesions; Affect; Belief; Biochemical; Biological Models; Biotin; CRISPR/Cas technology; Cell Shape; Cells; Chemicals; Color; Cyclic AMP-Dependent Protein Kinases; Cytoplasm; Cytoskeleton; Data; Dominant-Negative Mutation; Dynein ATPase; Elements; Filament; Focal Adhesions; Funding; Genes; Geometry; Goals; Image; In Vitro; Individual; Intermediate Filaments; Intracellular Transport; Invaded; Kinesin; Knock-out; Label; Literature; Mammalian Cell; Maps; Measures; Mechanics; Melanophores; Melanosomes; Membrane; Mesenchymal; Microfilaments; Microtubules; Mitochondria; Molecular; Motor; Movement; Organelles; Phosphorylation; Physiological; Pigments; Post-Translational Protein Processing; Proteins; Protocols documentation; Regulation; Reporter; Role; Shapes; Signal Transduction; Site; Structure; Substrate Interaction; System; Testing; Total Internal Reflection Fluorescent; Transmembrane Transport; Validation; Vimentin; cell motility; inhibitor/antagonist; link protein; member; nestin protein; tool

Project Summary—Project 2 (Gelfand) The goal of this proposal is to study dynamic interactions of vimentin intermediate filaments with two other components of the cytoskeleton, microtubules and actin microfilaments, as well as interactions of VIF with membrane organelles. We will study how intermediate filaments move along microtubules and identify microtubule motors that power this movement. We will determine biochemical basis of vimentin interactions with microtubule motors and identify molecular mechanisms involved in the regulation of these interactions, such as posttranslational modifications of vimentin. We will also find molecular mechanisms of vimentin interaction with actin microfilaments and their bundles and with components of focal adhesions. We will test if interactions of VIF with focal adhesions affect stability of cell-substrate interactions and how vimentin in focal adhesions modulates cell motility. We will identify molecular linkers between actin and intermediate filaments and study functional implications of this association. We will also find how intermediate filaments invade focal adhesions, which focal adhesion proteins link them in place and how intermediate filaments regulate adhesion turnover. Finally, the role of vimentin filaments in transport of membrane organelles will be investigated using two model systems, mitochondria and pigment organelles (melanosomes) in melanophores, because both of these organelles contain bound PKA and PKA-dependent phosphorylation is likely regulated in concert with intermediate filament dynamics and organelle transport.

项目摘要 - 项目 2 (Gelfand) 该提案的目标是研究波形蛋白中间丝与其他两种的动态相互作用 细胞骨架、微管和肌动蛋白微丝的组成部分，以及 VIF 与 膜细胞器。我们将研究中间丝如何沿着微管移动并识别 为这种运动提供动力的微管马达。我们将确定波形蛋白相互作用的生化基础 与微管马达并确定参与调节这些相互作用的分子机制， 例如波形蛋白的翻译后修饰。我们还将发现波形蛋白的分子机制 与肌动蛋白微丝及其束以及与粘着斑成分的相互作用。我们将测试是否 VIF 与粘着斑的相互作用影响细胞-基质相互作用的稳定性以及波形蛋白在粘着斑中的作用 粘附调节细胞运动。我们将识别肌动蛋白和中间丝之间的分子接头 并研究该关联的功能含义。我们还将发现中间丝如何侵入焦点 粘连，哪些粘着斑蛋白将它们连接到位以及中间丝如何调节粘连 周转。最后，将使用以下方法研究波形蛋白丝在膜细胞器运输中的作用 两个模型系统，线粒体和黑素细胞中的色素细胞器（黑​​素体），因为两者 这些细胞器含有结合的 PKA，并且 PKA 依赖性磷酸化可能与 中间丝动力学和细胞器运输。