Microtubule dynamics and cellular pattern formation

微管动力学和细胞模式形成

• 批准号: 7575804
• 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/7575804
• 关键词: Animals; Binding; Biochemistry; Biogenesis; Cataloging; Catalogs; Cell Cycle; Cell Nucleus; Cell Polarity; Cell physiology; Cells; Centrosome; Complex; Coupled; Cytokinesis; Cytoskeleton; Disease; Epithelial Cells; Exhibits; Fission Yeast; Human; Image Analysis; Interphase; Iran; 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; protein complex; 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.

微管细胞骨架在细胞过程中是必不可少的，如有丝分裂、细胞器运输和 细胞的极性。微管的关键组织者是微管组织中心(MTOC)。所有MTOC 由多个蛋白质复合体组成，共有三个一般性质：a)它们成核 微管。B)它们将微管排列成功能模式。以及c)它们将 微管连接到适当的细胞器靶标。近年来，定位于分子的分子 中心体是动物细胞中主要的MTOC，已被编目，并取得了很大进展 了解g-微管蛋白环复合体(g-turc)位于中心体的机制 有核的微管。然而，大多数细胞质G-turc并不位于中心体，它们的 细胞功能尚不清楚。此外，当正则中心体排列径向阵列时 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--有线形的微管阵列，这些微管没有附着在细胞核上。 产生微管线性阵列的机制是未知的，这是本文的主题 研究提案。 我的实验室最近发现了ase1+和mto2+，它们的基因产物定位于三种不同的MTOC。 Aselp在微管线形排列中起关键作用，而mto2p在微管中起关键作用。 成核作用。现在我们将重点分析aselp和mto2p在组织线性数组中的作用 微管。 这项建议将把酵母遗传学、生物化学和分子生物学与定量光学相结合 FRAP和光钳等显微镜方法研究aselp和mto2p在脑内的作用 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，进化守恒将 使我们在分裂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，并可能有助于我们理解由MTOC的病理引起的疾病 构成和功能。