Microtubule dynamics and cellular pattern formation

微管动力学和细胞模式形成

• 批准号: 7049791
• 负责人: PHONG T TRAN
• 金额: $ 27.48万
• 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/7049791
• 关键词: Schizosaccharomyces pombe; biological signal transduction; cell component structure /function; cell cycle; fluorescence recovery after photobleaching; fungal genetics; fungal proteins; microtubule associated protein; microtubules; molecular assembly /self assembly; phosphorylation; protein protein interaction; tubulin

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）：微管细胞骨架对于细胞过程（如有丝分裂、细胞器运输和细胞极性）至关重要。微管的主要组织者是微管组织中心（MTOC）。所有的MTOC都由多蛋白复合物组成，并且共有三个一般性质：a）它们使微管成核。B）它们将微管排列成功能模式。c）它们将微管附着在适当的细胞器目标上。近年来，定位于中心体（动物细胞中的主要MTOC）的分子已被分类，并在理解g-微管蛋白环复合物（g-TuRC）定位于中心体的微管成核机制方面取得了很大进展。然而，大多数细胞质g-TuRC不位于中心体，其细胞功能是未知的。此外，虽然典型的中心体排列着与细胞核相连的微管的放射状阵列，但许多高度分化的细胞类型-神经元，肌管和极化上皮细胞-具有不与细胞核相连的微管的线性阵列。产生微管线性阵列的机制是未知的，这是本研究提案的主题。我的实验室最近鉴定了ase 1+和mto 2+，它们的基因产物定位于三种不同的MTOC。ase 1 p在微管的线性排列中起关键作用，而mto 2 p在微管成核中起关键作用。现在我们将集中讨论ase 1 p和mto 2 p在组织微管线性阵列中的作用。该提案将联合收割机酵母遗传学、生物化学和分子生物学与FRAP和光镊等定量光学显微镜方法相结合，研究ase 1 p和mto 2 p在组织线性微管阵列中的作用。我们的研究将提供新的见解的分子机制的基础上的线性微管阵列的生物成因。此外，进化保守性将使我们在裂变酵母中的发现与我们对人类细胞中类似保守结构的理解高度相关，并可能有助于我们对MTOC形成和功能病理学引起的疾病的理解。