Microtubule dynamics and cellular pattern formation

微管动力学和细胞模式形成

• 批准号: 7174848
• 负责人: PHONG T TRAN
• 金额: $ 26.73万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7174848
• 关键词: Animals; Binding; Biochemistry; Biogenesis; Cataloging; Catalogs; Cell Cycle; Cell Nucleus; Cell Polarity; Cell physiology; Cells; Centrosome; Class; Complex; Coupled; Cytokinesis; Cytoskeleton; Disease; Epithelial Cells; Exhibits; Fission Yeast; Human; Image Analysis; Interphase; Iran; Localized; Methods; Microscopy; Microtubule Bundle; Microtubule-Associated Proteins; Microtubule-Organizing Center; Microtubules; Minus End of the Microtubule; Mitosis; Molecular; Molecular Biology; Molecular Motors; Muscle Fibers; Neurons; Optics; Organelles; Organism; Pathology; Pathway interactions; Pattern; Pattern Formation; Play; Plus End of the Microtubule; Property; Proteins; Radial; Recruitment Activity; Regulation; Research Personnel; Research Proposals; Resolution; Role; Specificity; Structure; Tubulin; cell type; insight; laser tweezer; member; mutant; programs; spindle pole body; yeast genetics

DESCRIPTION (provided by applicant): The microtubule cytoskeleton is essential for cellular processes such as mitosis, organelle transport, and cell polarity. The key organizer of microtubules is the microtubule organizing center (MTOC). All MTOCs are composed of multi-protein complexes and share three general properties: a) They nucleate microtubules. b) They arrange the microtubules into functional patterns. And c) They attach the microtubules to their proper organelle targets. In recent years the molecules that are localized to the centrosome, the primary MTOC in animal cells, have been catalogued and much progress has been made in understanding the mechanism by which the g-tubulin ring complex (g-TuRC) located at the centrosome nucleate microtubules. However, most cytoplasmic g-TuRCs are not located at the centrosome, and their cellular functions are unknown. Furthermore, while the canonical centrosome arranges radial arrays of microtubules which are attached to the nucleus, many highly differentiated cell types - neurons, myotubes, and polarized epithelial cells - have linear arrays of microtubules which are not attached to the nucleus. The mechanisms which generate linear arrays of microtubules are unknown and is the subject of this research proposal. My lab recently identified ase1+ and mto2+, whose gene products localize to the three different MTOCs. Ase1p plays key roles in linear arrangement of microtubules; and mto2p plays key roles in microtubule nucleation. And we will now focus on dissecting the roles of ase1p and mto2p in organizing linear arrays of microtubules. This proposal will combine yeast genetics, biochemistry, and molecular biology with quantitative optical microscopy methods such as FRAP and optical tweezers to study the role of ase1p and mto2p in organizing linear microtubule arrays. Our studies will provide new insights into the molecular mechanism which underlie the biogenesis of linear microtubule arrays. Furthermore, evolutionary conservation will make our findings in fission yeast highly relevant to our understanding of similar conserved structures in human cells, and may contribute to our understanding of disease arising from the pathology of MTOC formation and function.

描述（由申请人提供）：微管细胞骨架对于有丝分裂，细胞器转运和细胞极性等细胞过程至关重要。微管的主要组织者是微管组织中心（MTOC）。所有MTOC均由多蛋白质复合物组成，并具有三个一般特性：a）它们成核微管。 b）它们将微管排列为功能模式。 c）它们将微管连接到适当的细胞器靶标。近年来，局部在中心体的分子（动物细胞中的主要MTOC）已经分类，并且在理解位于中心体核定核微管的G-Tubulin环复合物（G-Turc）的机制方面已经取得了很多进展。然而，大多数细胞质G-turcs并不位于中心体，它们的细胞功能尚不清楚。此外，尽管规范的中心体排列了附着在细胞核上的微管的径向阵列，但许多高度分化的细胞类型（神经元，肌管和偏振上皮细胞）具有未连接到核的微管的线性阵列。生成微管线性阵列的机制尚不清楚，并且是该研究建议的主题。我的实验室最近确定了ASE1+和MTO2+，其基因产物本地化于三种不同的MTOC。 ASE1P在微管的线性排列中扮演关键角色； MTO2P在微管成核中起关键作用。现在，我们将专注于解剖ASE1P和MTO2P在组织微管线性阵列中的作用。该建议将结合酵母遗传学，生物化学和分子生物学与定量光学显微镜方法，例如FRAP和光学镊子，以研究ASE1P和MTO2P在组织线性微管阵列中的作用。我们的研究将提供有关线性微管阵列生物发生的分子机制的新见解。此外，进化保护将使我们在裂变酵母中的发现与我们对人类细胞中类似的保守结构的理解高度相关，并可能有助于我们对MTOC形成和功能的病理产生的疾病的理解。