Regulation of Sperm Cell Differentiation in C. elegans

线虫精子细胞分化的调控

• 批准号: 9073200
• 负责人: CRAIG W LAMUNYON
• 金额: $ 10.88万
• 依托单位: CALIFORNIA STATE POLY U POMONA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9073200
• 关键词: Affect; Alzheimer' s Disease; Appearance; Binding Sites; Bioinformatics; Biological Models; CRISPR/Cas technology; Caenorhabditis elegans; Cell Differentiation process; Cell division; Cells; Characteristics; Collection; Complex; DYSF gene; Data; Disease; Event; Exocytosis; FPS-FES Oncogene; Family; Gene Expression Regulation; Genes; Goals; Homologous Gene; Human; Investigation; Knowledge; Lead; Location; Malignant Neoplasms; Maps; Methods; Molecular; Muscular Dystrophies; Mutation; Mutation Analysis; One-Step dentin bonding system; Organelles; Outcome; Pathway interactions; Positioning Attribute; Procedures; Process; Protein Activation Pathway; Protein Inhibition; Proteins; Proto-Oncogenes; Public Health; Regulation; Regulator Genes; Reporter; Research; Role; Set protein; Signal Pathway; Signal Transduction; Signaling Protein; Spermatids; Spermiogenesis; Structure; Testing; Vesicle; Work; base; casein kinase; cell motility; design; gene function; gene product; genetic analysis; genetic regulatory protein; genome sequencing; human disease; member; mutant; premature; presenilin; prevent; public health relevance; sperm cell; tau-tubulin kinase; whole genome

 DESCRIPTION (provided by applicant): Major cellular events are typically regulated through the interaction of promoting and inhibiting factors, but an understanding of all the antagonistic factors and their interactions is generally incomplete for most cellular events. This proposal focuses on the antagonistic regulation of spermatid activation C. elegans. Also called spermiogenesis, this wholesale cellular reorganization involves regulated vesicle exocytosis, pseudopod formation, and the induction of motility, transforming spherical spermatids into amoeboid spermatozoa. Spermiogenesis occurs when spermatids encounter an activation signal that is transduced into the cell via a signaling complex of five gene products. Spermiogenesis is inhibited directly by the protein SPE-6, while another set of proteins contribute to the formation of a specialized organelle that also inhibits spermiogenesis: the Fibrous Body-Membranous Organelle (FB-MO). With both promoting and inhibiting factors, spermiogenesis in C. elegans is an ideal model system for investigation of antagonistic regulation. Further, preliminary data show that activation and inhibition converge on the SPE-6 protein. While five of the gene products involved in the regulation of sperm activation have been identified, a collection of mutations defining additional regulatory genes remains to be investigated, so knowledge of the antagonistic regulation of spermiogenesis is incomplete. Thus, there is an important need to uncover more of the regulatory proteins and to investigate their interactions. The long-term goal of the research is to gain a more comprehensive understanding of the antagonistic regulation of sperm activation in C. elegans. The central hypothesis of the research is that the signal promoting spermiogenesis is transduced into the cell where it relieves inhibition by down-regulating SPE-6 and by altering FB-MO function. The rationale for the proposed research is that it will enable identification of more of the proteins involved in spermiogenesis regulation, and it will contribute to knowledge of the function, localization, and interactions of these proteins. The expected outcomes of the proposed research are that 3 to 5 new spermiogenesis regulation genes will be identified and their functional roles will be established. Further, the role of SPE-6 protein as the intersection between signaling and inhibition will be determined. These results are expected to have a positive impact, because they will provide a more comprehensive understanding of the antagonistic regulation.

 描述（由申请人提供）：主要细胞事件通常通过促进因子和抑制因子的相互作用来调节，但是对于大多数细胞事件来说，对所有拮抗因子及其相互作用的理解通常是不完整的。该提案重点关注精子细胞的拮抗调节。激活秀丽隐杆线虫，这种大规模的细胞重组涉及调节的囊泡胞吐作用、伪足形成和运动诱导，将球形精子细胞转化为变形虫。当精子细胞遇到通过五种基因产物的信号复合物转导到细胞中的激活信号时，精子发生就会被蛋白质 SPE-6 直接抑制，而另一组蛋白质则有助于形成特殊的细胞器。也抑制精子发生：纤维体膜细胞器 (FB-MO) 具有促进和抑制因子，秀丽隐杆线虫的精子发生是研究精子发生的理想模型系统。此外，初步数据表明，激活和抑制集中在 SPE-6 蛋白上，虽然已经鉴定出参与精子激活调节的五种基因产物，但定义其他调节基因的一系列突变仍有待研究。因此，对精子发生的拮抗调节的了解是不完整的，因此，迫切需要发现更多的调节蛋白并研究它们的相互作用。该研究的长期目标是获得对拮抗调节的更全面的了解。精子的激活C.该研究的中心假设是，促进精子发生的信号被转导到细胞中，通过下调 SPE-6 和改变 FB-MO 功能来减轻抑制。这项研究的基本原理是，它将能够进行鉴定。更多参与精子发生调控的蛋白质，这将有助于了解这些蛋白质的功能、定位和相互作用。拟议研究的预期结果是，将鉴定和发现 3 至 5 个新的精子发生调控基因。此外，还将确定 SPE-6 蛋白作为信号传导和抑制之间的交叉点的作用，这些结果预计将产生积极的影响，因为它们将提供对拮抗调节的更全面的了解。