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。该提案的重点是线虫精子细胞激活的拮抗调节。这种大规模细胞重组也称为精子发生，涉及受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精子。当精细胞遇到激活信号时，精子发生就会发生，该激活信号通过五种基因产物的信号复合物转导到细胞中。精子发生直接受到蛋白质 SPE-6 的抑制，而另一组蛋白质则有助于形成也抑制精子发生的特殊细胞器：纤维体膜细胞器 (FB-MO)。线虫精子发生同时具有促进和抑制因子，是研究拮抗调节的理想模型系统。此外，初步数据表明激活和抑制作用集中在 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还不完整。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更全面地了解秀丽隐杆线虫精子激活的拮抗调节。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 功能来缓解抑制。拟议研究的基本原理是，它将能够识别更多参与精子发生调节的蛋白质，并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，将鉴定出 3 至 5 个新的精子发生调控基因，并确定它们的功能作用。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影响，因为它们将提供对拮抗调节的更全面的理解。