The role of the cytoskeleton in germ cell apoptosis in C. elegans

细胞骨架在秀丽隐杆线虫生殖细胞凋亡中的作用

• 批准号: 8720793
• 负责人: JAMES R PRIESS
• 金额: $ 32万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8720793
• 关键词: Address; Adult; Aging; Animals; Apoptosis; Apoptotic; Autoimmune Diseases; Biological Models; Caenorhabditis elegans; Cell Nucleus; Cell Polarity; Cells; Cessation of life; Cytoplasm; Cytoskeleton; Development; Development Polarity; Digestion; Disease; Embryonic Development; Excision; Genetic Models; Germ Cells; Giant Cells; Goals; Gonadal structure; Grant; Health; Image; Immune; Individual; Left; Life; Malignant Neoplasms; Microtubule-Organizing Center; Microtubules; Mitochondria; Molecular; Molecular Genetics; Nerve Degeneration; Normal Cell; Organelles; Pathway interactions; Phosphotransferases; Physiological; Play; Process; Recycling; Regulation; Resistance; Role; Somatic Cell; Stress; System; Tissues; base; human disease; inhibitor/antagonist; mutant; prevent; programs; public health relevance; research study

DESCRIPTION (provided by applicant): Programmed cell death or apoptosis is a fundamental, highly conserved pathway in animal development, and plays critical roles in normal health, as well as in aging and disease. Apoptotic cells must shut themselves down while leaving surrounding cells and tissues intact, and part of this process involves changes in the cytoskeleton of the apoptotic cells. Studies in the genetic model system C. elegans identified many of the key molecules that regulate and execute apoptosis, and this grant uses C. elegans as a system to understand the apoptotic regulation of the microtubule cytoskeleton. The study focuses on adult gonads, where about 50% of germ cells normally undergo apoptosis. The gonad is an example of a syncytial tissue, where individual "cells" maintain small cytoplasmic connections with neighboring cells. In a syncytium, the apoptotic removal of nuclei and cytoplasm must be tightly controlled to prevent death of the whole. The connections between "cells" present the possibility that part or all of the apoptotic cytoplasm might be transferred intact to the syncytium, rather than simply being degraded and recycled as metabolites. This grant examines how the normal microtubule cytoskeleton is dismantled during germ cell apoptosis, and how the new cytoskeleton is organized. It addresses the fate of cytoplasmc components of the apoptotic cell, and whether the new MT cytoskeleton contributes to the transfer of cytoplasm. Through either transfer or digestion, the apoptotic cell ultimately shrinks its cytoplasm, dismantles its cytoskeleton entirely, and is absorbed by other cells. This study identifies a role for the conserved kinase PAR-1 in the final steps of apoptotic remodeling, and addresses possible steps that might be regulated by PAR-1 activity.

描述（由申请人提供）：程序性细胞死亡或细胞凋亡是动物发育中一种基本的、高度保守的途径，在正常健康以及衰老和疾病中起着关键作用。凋亡细胞必须关闭自己，同时保持周围细胞和组织的完整性，这一过程的一部分涉及凋亡细胞的细胞骨架的变化。遗传模型系统C. elegans发现了许多调节和执行细胞凋亡的关键分子，这项资助使用了C. elegans作为一个系统来了解微管细胞骨架的凋亡调控。这项研究的重点是成年性腺，其中约50%的生殖细胞通常会发生凋亡。性腺是合胞体组织的一个例子，其中单个“细胞”与相邻细胞保持小的细胞质连接。在合胞体中，必须严格控制细胞核和细胞质的凋亡去除，以防止整体死亡。“细胞”之间的连接提出了这样的可能性，即部分或全部凋亡细胞质可能完整地转移到合胞体中，而不是简单地被降解和作为代谢物再循环。该基金研究了在生殖细胞凋亡过程中，正常的微管细胞骨架是如何被拆除的，以及新的细胞骨架是如何组织的。它解决了凋亡细胞的胞质组分的命运，以及新的MT细胞骨架是否有助于细胞质的转移。通过转移或消化，凋亡细胞最终收缩其细胞质，完全破坏其细胞骨架，并被其他细胞吸收。本研究确定了保守激酶PAR-1在凋亡重塑的最后步骤中的作用，并讨论了可能受PAR-1活性调节的可能步骤。