Cytokinesis in Caenorhabditis Elegans

秀丽隐杆线虫的细胞分裂

• 批准号: 7003815
• 负责人: John Graham White
• 金额: $ 29.42万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7003815
• 关键词: Caenorhabditis elegans; RNA interference; cell component structure /function; cell cycle; cell membrane; cell proliferation; cellular pathology; cytogenetics; early embryonic stage; electron microscopy; endocytosis; fluorescence microscopy; gene expression; gene interaction; genetic regulation; genetic screening; green fluorescent proteins; immunoelectron microscopy; light microscopy; membrane permeability; mitotic spindle apparatus; protein transport; yeast two hybrid system

This project seeks to gain an understanding of the fundamental process of animal cell cleavage (cytokinesis). It has recently become apparent that animal cell cytokinesis is executed in two phases: the ingression of a circumferential cleavage furrow and the final breaking and resealing of membrane at the residual intercellular bridge (scission). The investigations will focus on the mechanisms that are used to execute scission in the early development of the nematode Caenorhabditis elegans. Prevoius studies have shown that the process of scission requires the presence of the mid-body of the mitotic spindle and targetedocytosis in the region of the cleavage furrow. It is proposed to use functional suppression of genes that encode components of the mid-body coupled with cytological examination of the resultant phenotype in vivo as a means of identifying the role of these components in the machinery that executes scission. We are focusing on two genes that have critical roles in scission, spd-1 and Y18D10A. 17. We will determine how these genes interact with known components of the scission machinery and will also seek other interacting proteins in order to uncover the genetic pathways used in scission. These studies will be complemented by studies of membrane trafficking to the region of the intercellular bridge at the time of scission. Through the use of compartment-specific probes used in conjunction with in vivo imaging, the source of the membrane that is targeted to the late cleavage furrow during scission will be determined. The in vivo observations of the late cytokinetic furrow using the light microscope will be complemented by studies using electron microscopy in order to visualize the ultrastructural interrelationship between the cytoskeletal components of the mid-body and membrane traffic. Cytokinesis is a fundamental cellular process, and as such its malfunction could result in pathologies. If a cleavage fails, any subsequent cleavage of the resulting multipolar cell would result in anuploid daughter cells, which could lose normal growth controls and proliferate inappropriately. For example, filaments of asbestos as are known to interfere with cleavage furrows. This mechanism could explain the carcinagenetic effects of asbestos exposure.

该项目旨在了解动物细胞裂解的基本过程 （细胞因子）。最近显而易见的是，动物细胞细胞因子分为两个阶段：呈圆周裂解沟的感染以及在残留细胞间桥（SCESION）处的膜的最终破裂和重新密封。调查将集中于在线虫秀丽隐杆线虫的早期发育中用于执行分裂的机制。前乌斯研究表明，分裂过程需要在裂解沟区域中存在有丝分裂纺锤体和靶向性细胞增多症的中体。有人建议使用对中体的组件的功能抑制，结合体​​内的组成型组件以及对所得表型的细胞学检查作为识别这些成分在执行分数的机械中的作用的手段。我们专注于两个在SPD-1和Y18D10A中具有关键作用的基因。 17。我们将确定这些基因如何与Scission机械的已知成分相互作用，还将寻求其他相互作用的蛋白质，以发现Scission中使用的遗传途径。这些研究将通过对分裂时对细胞间桥梁区域的膜运输的研究进行补充。通过 将使用与体内成像结合使用的隔室特异性探针，该探针将确定针对晚期裂解的膜的来源。使用电子显微镜的研究将补充使用光学显微镜的晚期细胞动力沟的体内观察，以可视化中体和膜流量的细胞骨架成分之间的超微结构相互关系。 细胞因子是一种基本的细胞过程，因此其故障可能导致病理。如果裂解失败，随后的多极细胞的任何随后切割都会导致肌倍性子细胞，这可能会失去正常的生长控制并不适当地增殖。例如，已知的石棉细丝会干扰裂解沟。这种机制可以解释石棉暴露的癌作用。