Microtubule dynamics and cellular pattern formation

微管细胞骨架对于细胞过程如有丝分裂、细胞器运输和细胞分裂是必不可少的。 细胞极性微管的主要组织者是微管组织中心（MTOC）。所有MTOC 由多蛋白质复合物组成，共有三个一般性质： 微管B）它们将微管排列成功能模式。c）他们把 微管到其适当的细胞器目标。近年来，定位于分子的 中心体是动物细胞中最主要的MTOC，目前已被分类并取得了很大进展 在理解g-微管蛋白环复合物（g-TuRC）位于中心体的机制方面， 有核微管然而，大多数细胞质g-TuRC不位于中心体，并且它们的 细胞功能是未知的。此外，虽然典型的中心体排列放射状阵列， 微管附着在细胞核上，许多高度分化的细胞类型-神经元，肌管， 和极化上皮细胞-具有不附着于细胞核的微管的线性阵列。 产生微管线性阵列的机制是未知的，这是本论文的主题。 研究提案。 我的实验室最近鉴定了ase1+和mto2+，它们的基因产物定位于三种不同的MTOC。 aselp在微管的线性排列中起关键作用，mto2p在微管的线性排列中起关键作用。 成核现在我们将集中讨论aselp和mto2p在组织线性阵列中的作用。 微管 该建议将联合收割机酵母遗传学、生物化学和分子生物学与定量光学 显微镜方法，如FRAP和光学镊子，以研究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 这是线性微管阵列生物发生的基础。此外，进化保守将 使我们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，并可能有助于我们理解的疾病所产生的病理MTOC 形成和功能。

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.