Microtubule dynamics and cellular pattern formation

微管动力学和细胞模式形成

• 批准号: 7347587
• 负责人: PHONG T TRAN
• 金额: $ 26.76万
• 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/7347587
• 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

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. Aselp 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 aselp 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 aselp 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.

微管细胞骨架对于诸如有丝分裂，细胞器转运和 细胞极性。微管的主要组织者是微管组织中心（MTOC）。所有mtocs 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）他们附着 微管达到其适当的细胞器靶标。近年来，本地化的分子 中心体是动物细胞中的主要MTOC，已分类，并且已经取得了很多进展 在理解g-微管蛋白环复合物（G-turc）位于中心体的机制时 成核微管。但是，大多数细胞质G-turcs都不位于中心体，它们的 细胞功能未知。此外，典型的中心体安排了径向阵列 附着在细胞核上的微管，许多高度分化的细胞类型 - 神经元，肌管，， 和极化的上皮细胞 - 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未知，是这样的主题 研究建议。 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。 Aselp在微管的线性排列中扮演关键角色； MTO2P在微管中扮演关键角色 成核。现在，我们将专注于剖析Aselp和MTO2P在组织线性阵列中的作用 微管。 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）研究Aselp和MTO2P在 组织线性微管阵列。我们的研究将为分子机制提供新的见解 这是线性微管阵列的生物发生的基础。此外，进化保护将 在裂变酵母中的发现与我们对类似保守结构的理解高度相关 人类细胞，并可能有助于我们对MTOC病理产生的疾病的理解 形成和功能。