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Regulation and Function of Intermediate Filaments in Cell Mechanics

细胞力学中中间丝的调节和功能

基本信息

批准号：
8142481
负责人：
ROBERT D GOLDMAN
金额：
$ 52.66万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
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：
2011-06-15 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8142481
关键词：
Actins Adult Affect Bulla C-terminal Cardiomyopathies Cell Shape Cells Chemicals Connecticut Cytoskeleton Defect Development Disease Disease Attributes Electrons Elements Embryo Event Exhibits Fibroblasts Figs - dietary Filament Fracture Genes Goals Histocompatibility Testing Housekeeping Hydrolysis Image In Vitro Intermediate Filament Gene Intermediate Filament Proteins Intermediate Filaments Lamins Lead Length Life Link Mammalian Cell Mechanical Stress Mechanics Microfilaments Microscopic Microtomy Microtubules Molecular Motors Movement Muscular Dystrophies Mutation Nucleotides Phosphorylation Play Premature aging syndrome Process Program Research Project Grants Property Regulation Research Role Shapes Signal Transduction Staging Stress Stretching Structural Protein Structure Symptoms System Techniques Testing Time Tissues Transducers Tubulin Universities Vimentin Width X-Ray Crystallography base cell motility cell type dimer disease-causing mutation experience flexibility human disease insight programs protein expression response retinal rods skin disorder soft tissue

项目摘要

In this Program Project Grant our overarching hypothesis is that alterations in the assembly states and mechanical properties of cytoskeletal IF, specifically the type III IF composed of vimentin (VIF), play important roles in regulating the micromechanical properties of cells in response to mechano- and chemosignalling. These studies are critically important as IF are major elements of the cytoskeletal system of mammalian cells and yet their specific functions in cell motility remain unknown. The 6 Project Leaders, and their research aims are as follows: R. Goldman, Northwestern University, will determine how the vimentin IF (VIF) system changes in response to mechanical and chemical signals, and will purify and characterize the vimentin precursors that form as VIF assemble and disassemble. V. Gelfand, Northwestern University will determine the relationship between VIF with microtubules and actin filaments, identify the molecular motors responsible for translocating VIF precursors, and investigate how VIF affect cytoskeletal dynamics and microtubule (MT) dynamics. G. Danuser, Harvard University, will test the hypotheses that VIF network formation involves a spatially distributed assembly line, that this process involves molecular motors, and that VIF network assembly modulates assembly of MT and microfilaments (MF). D. Weitz, Harvard University, will determine the micromechanical properties of in vitro asembled VIF networks prepared from purified vimentin, native VIF networks isolated from cells and in living cells. P. Janmey, University of Pennsylvannia, will determine how the VIF network contributes to the micromechanical properties of living cells and how this changes in response to substrate stiffness and external forces. P. Burkhard, University of Connecticut, will use biophysical techniques and X-ray crystallography to determine the structure and biophysical properties of the vimentin dimer and study the formation of VIF assembly intermediates. In all of these studies, the regulatory function of different posttranslational phosphorylation events will be examined.

在本项目中，我们的总体假设是细胞骨架IF的组装状态和机械特性的改变，特别是由vimentin （VIF）组成的III型IF，在响应机械和化学信号传导时调节细胞的微机械特性方面发挥重要作用。