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首页> 外文学位 >Analysis of the mitotic spindle proteome reveals conserved cell division factors in Caenorhabditis elegans.
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Analysis of the mitotic spindle proteome reveals conserved cell division factors in Caenorhabditis elegans.

机译：对有丝分裂纺锤体蛋白质组的分析揭示了秀丽隐杆线虫中保守的细胞分裂因子。

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摘要

Cell division is important for many cellular processes including cell growth, reproduction, wound healing and stem cell renewal. Failures in cell division can lead to tumors and birth defects. Numerous proteins ensure the proper allocation of chromosomes to daughter cells in cell division. However, despite our knowledge about the main components in cell division, questions remain as to exactly how many factors play a role in cell division and what their functions are.;In this dissertation, I identified and profiled the mitotic spindle proteome in Chinese Hamster Ovary (CHO) cells for likely cell division candidates. The assembled mitotic spindle proteome totaled 1155 proteins, and profiling the spindle proteins by subcellular localization yielded 313 cell division candidates in the categories of membrane-associated, microtubule-associated, actin-associated and unknown localization. Additionally, comparative proteomics was performed to the previously published CHO midbody proteome and the HeLa mitotic spindle proteome.;In the subsequent study, I identified cell division factors from the initial list of cell division candidates from the mitotic spindle proteome. I found that 72% of mitotic spindle candidates had homologs in Caenorhabditis elegans and that 34 out of the 143 homologs tested were required for embryonic survival in C. elegans. Of the 34 embryonic lethal genes, 21 were determined to be necessary for cell division in a visual screen. A membrane protein whose homologs are involved in glycosylation, OSTD-1, was characterized further. Depletion of OSTD-1 resulted in cell cycle defects, spindle orientation defects, aberrant karyomere fusion, extra cleavage furrows, alterations in cleavage furrow positioning and cytokinesis failures. OSTD-1 also may play a role in ER morphology during mitosis.;Together, my work identified OSTD-1 as a cell division factor from the mitotic spindle proteome and offered an initial characterization of its role in cell division. My work reinforced the connections between membrane proteins, glycosylation and cell division in C. elegans, which is likely conserved in other organisms.
机译：细胞分裂对于许多细胞过程都很重要，包括细胞生长，繁殖，伤口愈合和干细胞更新。细胞分裂失败会导致肿瘤和先天缺陷。许多蛋白质可确保染色体在细胞分裂中正确分配给子细胞。然而，尽管我们了解细胞分裂的主要成分，但仍然存在关于到底有多少因素在细胞分裂中起作用及其作用的问题。；在本文中，我鉴定并概述了中国仓鼠卵巢的有丝分裂纺锤体蛋白质组。 （CHO）细胞作为可能的细胞分裂候选者。组装的有丝分裂纺锤体蛋白质组共1155种蛋白质，通过亚细胞定位对纺锤体蛋白质进行谱分析，可得到313种细胞分裂候选物，分别属于膜相关，微管相关，肌动蛋白相关和未知的定位。此外，对以前发表的CHO中体蛋白质组和HeLa有丝分裂纺锤体蛋白质组进行了比较蛋白质组学。在随后的研究中，我从有丝分裂纺锤体蛋白质组的候选细胞分裂初始列表中鉴定了细胞分裂因子。我发现72％的有丝分裂纺锤体候选对象在秀丽隐杆线虫中具有同源物，而在测试的143个同源物中，有34个对于秀丽隐杆线虫的胚胎存活是必需的。在34个胚胎致死基因中，有21个被确定是在可视屏幕中进行细胞分裂所必需的。进一步鉴定了其同系物参与糖基化的膜蛋白OSTD-1。 OSTD-1的消耗导致细胞周期缺陷，纺锤体定向缺陷，异常的核小体融合，额外的分裂沟，分裂沟位置的改变和胞质分裂失败。 OSTD-1在有丝分裂过程中也可能在ER形态中起作用。；总的来说，我的研究确定OSTD-1是有丝分裂纺锤体蛋白质组中的细胞分裂因子，并初步表征了它在细胞分裂中的作用。我的工作加强了秀丽隐杆线虫的膜蛋白，糖基化和细胞分裂之间的联系，这在其他生物中可能是保守的。

著录项

  • 作者

    Bonner, Mary Kate.;

  • 作者单位

    The University of Wisconsin - Madison.;

  • 授予单位 The University of Wisconsin - Madison.;
  • 学科 Genetics.;Cellular biology.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 250 p.
  • 总页数 250
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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