L-SELECTIN AND TESTICULAR CELL INTERACTIONS

L-选择素和睾丸细胞的相互作用

• 批准号: 6874407
• 负责人: CLARKE F MILLETTE
• 金额: $ 22.76万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-23 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6874407
• 关键词: Mammalia; Sertoli cells; actins; cell adhesion; cell migration; cytoskeleton; epithelium; germ cells; guanosinetriphosphatases; male; molecular assembly /self assembly; protein localization; protein protein interaction; receptor binding; selectins; spermatogenesis; testis; tight junctions; tissue /cell culture

DESCRIPTION: (Adapted from the applicant's abstract) Molecular mechanisms mediating testicular cell adhesions and intraepithelial germ cell translocations remain largely unexplored. In this proposal, the investigator hypothesizes that L-selectin expressed on the surfaces of Sertoli cells is directly involved in germ cell-Sertoli cell adhesion and germ cell translocation in the seminiferous epithelium. He proposes that binding of L-selectin to fucosylated ligands on germ cells triggers a signaling pathway involving small GTPases which alter actin polymerization and thus mediate rearrangements of the Sertoli cell cytoskeleton which are necessary for proper movement of germ cells through the epithelium. Four SA's are proposed. First, the hypothesis that transcription and translation of Sertoli cell L-selectin are related to important changes in Sertoli cells necessary for spermatogenesis will be tested by looking for stage-specific expression of L-selectin and by examining its developmental timing, particularly as related to Sertoli junction formation. Second, the investigator will ask whether L-selectin interacts with cytoskeletal-associated proteins, whether it is partially cleaved by its activation, and whether this causes alteration of the activity of small GTPases, thus regulating actin polymerization. In the third aim, the investigator will test the hypothesis that testicular L-selectin modulates Sertoli cell tight junctions via its interaction with the cytoskeleton and the resultant changes in GTPase activity. Finally, the specific fucosylated Lewis-like molecules on germ cells which serve as L-selectin ligands will be identified and the PI will determine whether exposure of Sertoli cells to these compounds causes changes in their small GTPases, rearrangements in the actin cytoskeleton and changes in tight junctions.

描述：（改编自申请人的摘要）分子机制 介导睾丸细胞粘附和上皮内生殖细胞 易位仍未开发。在此提案中，调查员 假设在Sertoli细胞表面表达的L-选择素是 直接参与生殖细胞辛酚细胞粘附和生殖细胞 在生精上皮中的易位。他提出了约束 L-选择素到生殖细胞上的岩藻糖基化配体触发信号通路 涉及改变肌动蛋白聚合并因此介导的小gtpases Sertoli细胞细胞骨架的重排是正确的 生殖细胞通过上皮运动。提出了四个SA。第一的， Sertoli细胞L-选择素的转录和翻译的假设 与精子发生所需的Sertoli细胞的重要变化有关 将通过寻找L-选择素的特定阶段表达来测试 检查其发育时机，特别是与Sertoli Junction相关 形成。其次，研究者将询问L-选择素是否与 细胞骨架相关蛋白，无论其部分被其部分裂解 激活以及这是否导致小的活性改变 GTPases，从而调节肌动蛋白聚合。在第三个目标中 研究者将测试睾丸L-选择素调节的假设 Sertoli细胞通过与细胞骨架的相互作用和 最终的GTPase活性变化。最后，特定的岩藻糖基化 生殖细胞上的刘易斯样分子将是L-选择素配体的 确定的，PI将确定Sertoli细胞是否暴露于这些细胞 化合物导致其小GTPase的变化，肌动蛋白的重排 细胞骨架和紧密连接的变化。