Regulation of Coordination of Molecular Motors

分子马达协调的调节

• 批准号: 7999994
• 负责人: Vladimir I Gelfand
• 金额: $ 10.68万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-14 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7999994
• 关键词: ATP Hydrolysis; Actin-Binding Protein; Actins; Address; Affect; Binding; Biological Models; Cell division; Cells; Chemicals; Coupling; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cytoplasm; Data; Defect; Diffusion; Drosophila genus; Drosophila melanogaster; Dynein ATPase; Eukaryotic Cell; Goals; Image; In Vitro; Intermediate Filaments; Interphase; Kinesin; Latex Bead; Libraries; Life; Link; Macromolecular Complexes; Magnetism; Measures; Mediating; Melanophores; Melanosomes; Messenger RNA; Microfilaments; Microtubules; Molecular; Molecular Motors; Monitor; Motor; Motor Neurons; Movement; Mutate; Myosin ATPase; Neurodegenerative Disorders; Neurofibromatoses; Neurons; Normal Cell; Optics; Organelles; Pathway interactions; Phagocytes; Phagosomes; Phosphotransferases; Pigmentation physiologic function; Pigments; Positioning Attribute; Process; Proteins; RNA Interference; Rana; Regulation; Research Personnel; Resolution; Role; Signal Transduction; Signaling Molecule; Slide; Source; Surface; System; Systems Analysis; Testing; Time; Tubulin; Vimentin; Viscosity; Work; Xenopus; Xenopus laevis; cell motility; design; feeding; in vivo; knock-down; laser tweezer; millisecond; motor control; mutant; organelle movement; overexpression; particle; permanent cell line; photoactivation; programs; protein complex; research study

DESCRIPTION (provided by applicant): Transport of organelles and macromolecular complexes through the cytoplasm is essential for every eukaryotic cell. This process is performed by motor proteins that use the chemical energy of ATP hydrolysis to move their cargo along microtubules and actin filaments. The spatial and temporal control of motor- dependent transport is critical for cell division, organelle transport and positioning, and the movement of mRNA and protein complexes within the cell. Defects in organelle transport and motor-associated proteins contribute or cause many neurodegenerative diseases, neurofibromatosis and defects of pigmentation. The goal of this proposal is to understand how multiple motors moving a cargo function together to achieve targeted and timely delivery of components in the cell. We want to know how the activity of multiple motors is coordinated in a cell and how these motors are regulated. Two biological models will be used for the proposed work. A permanent cell line of pigment cells (melanophores) from the frog Xenopus laevis will be used to study the regulation of movement. This is an ideal system for the analysis of regulation because the motors are well-characterized and movement of pigment organelles can be triggered by changes in cAMP concentration. Cultured neuronal and phagocytic cells from Drosophila melanogaster are extremely sensitive to protein knock-down by RNAi allowing for efficient functional analysis of components involved in motility and coordination of motors. This proposal has four specific aims: (i) to find the mechanisms of cross-talk between microtubule motors of the opposite polarity; (ii) to find if multiple motors of the same polarity make transport more efficient and determine to what extent movement of the microtubules contributes to cargo transport; (iii) to find how myosin motors, moving along a network of actin filaments, and intermediate filaments interacting with cargo, modulate long-range transport by microtubule motors; (iv) to find mechanisms of targeting signaling molecules to cargo organelles and the identity of components downstream of signaling molecules.

描述（由申请人提供）：细胞器和大分子复合物通过细胞质的运输对于每个真核细胞都是必不可少的。该过程是由运动蛋白使用的运动蛋白使用ATP水解的化学能将其货物沿微管和肌动蛋白丝移动的。运动依赖转运的空间和时间控制对于细胞分裂，细胞器的传输和定位以及细胞内mRNA和蛋白质复合物的运动至关重要。细胞器转运和与运动相关蛋白的缺陷会导致或引起许多神经退行性疾病，神经纤维瘤病和色素沉着缺陷。该提案的目的是了解多个电动机如何一起移动货物功能，以实现细胞中组件的有针对性和及时的交付。我们想知道如何在单元格中协调多个电动机的活性以及如何调节这些电动机。拟议的工作将使用两个生物模型。来自青蛙爪诺氏植物的色素细胞（黑色素细胞）的永久细胞系将用于研究运动的调节。这是分析调节的理想系统，因为电动机是特征良好的，色素细胞器的运动可以通过cAMP浓度的变化触发。来自果蝇的培养的神经元和吞噬细胞对RNAi的蛋白质敲低非常敏感，从而有效地对参与电动机的运动性和协调的组件进行有效的功能分析。该提案具有四个特定的目的：（i）找到相反极性的微管电动机之间的串扰机理； （ii）找到相同极性的多个电动机是否会提高运输效率，并确定微管的运动在多大程度上有助于货物运输； （iii）寻找肌球蛋白电动机如何沿肌动蛋白细丝网络以及与货物相互作用的中间细丝如何调节微管电动机的长距离运输； （iv）找到靶向信号分子到货物细胞器的机制以及信号分子下游的组件的身份。