Dynein independent roles for dynein light chain in meiotic progression

项目摘要 同源染色体配对和减数分裂联会是两者所必需的基本过程。 防止子代非整倍体和发育缺陷的卵子发生和精子发生。尽管 突触的重要性和高度保守性，在两性之间并不是每一个方面都是相同的。 异性配子物种已经进化出对减数分裂配对和联会的不那么严格或不同的调节 才能成功地传递他们的遗传信息。我的初步结果表明，雄性和雌性C. 在调节突触的启动过程中，优雅的人甚至对动力蛋白有不同的要求。动力蛋白依赖 已经提出了力量来测试潜在的同源匹配是正确的，并且一旦这已经被 建立，突触(SYP)蛋白在同源物之间启动。动力灯的击倒 链(DLC-1)在高温下导致远离染色质的SYP多复合体的形成 女性。出乎意料的是，在相同温度下，雄性DLC-1的耗尽显示出大体正常的突触。 更令人惊讶的是，动力蛋白重链和动力蛋白成分的突变体也没有表现出SYP 雌性减数分裂中的多复合体。这表明中存在之前未描述的DLC-1功能 突触启动。DLC-1的动力蛋白非依赖性功能有很多例子，包括稳定 或中断二聚体的相互作用。已经报道了DLC-1同源基因的共识结合基序，以及 在其中一个SYP蛋白中有一个潜在的结合基序。我推测DLC-1的功能是调节 SYP蛋白相互作用，直到验证正确配对。我进一步假设，男性雇佣一名 调节突触启动的替代方法。特定目的I研究DLC-1在女性中的作用 通过测试它是否与突触蛋白直接相互作用，以及DLC-1在雌性减数分裂中的相互作用将是 确认并测试了在突触启动中的作用。《特殊目的II》侧重于为什么男性不需要DLC-1 通过评估在配对的染色体中男性是否需要动力蛋白，并调查在配对的染色体中是否存在冗余 轻链在雄性减数分裂过程中进化。了解减数分裂调控中的性别差异 基因上易驯化的生物将帮助我们更好地了解人类的自然和疾病状态，这些状态会导致 非整倍体和减数分裂不孕症的发生率增加。

Project Summary Homologous chromosome pairing and meiotic synapsis are essential processes that are required in both oogenesis and spermatogenesis to prevent aneuploidy and developmental defects in offspring. Despite the importance and high conservation of synapsis, not every aspect is the same between the two sexes. Heterogametic species have evolved less stringent or differential regulation of meiotic pairing and synapsis in order to successfully pass on their genetic information. My preliminary results indicate that male and female C. elegans even have different requirements for dynein in regulating the initiation of synapsis. Dynein dependent forces have been proposed to test that a potential homolog match is correct, and once this has been established, synapsis (SYP) protein loading between the homologs initiates. Knockdown of the dynein light chain (DLC-1) at an elevated temperature results in SYP polycomplex formation away from chromatin in females. Unexpectedly, DLC-1 depletion in males at the same temperature shows grossly normal synapsis. Even more surprisingly, mutants in the heavy chain and dynactin components of dynein also do not show SYP polycomplexes in female meiosis. This indicates that there is a previously undescribed function for DLC-1 in synapsis initiation. There are many examples of dynein-independent functions for DLC-1, including stabilizing or interrupting dimer interactions. A consensus binding motif for the DLC-1 ortholog has been reported, and there is a potential binding motif in one of the SYP proteins. I hypothesize that DLC-1 functions to regulate SYP protein interactions until correct pairing has been verified. I further hypothesize that males employ an alternative method to regulate synapsis initiation. Specific Aim I investigates the role that DLC-1 has in female meiosis by testing if it interacts directly with synapsis proteins, and DLC-1 interactors in female meiosis will be identified and tested for a role in synapsis initiation. Specific Aim II focuses on why males do not require DLC-1 by assessing if males need dynein at all in pairing chromosomes, and investigate whether a redundancy in light chains evolved in male meiosis. Understanding such sex specific differences in meiotic regulation using a genetically tractable organism will help us better understand natural and disease states in humans that lead to an increased incidence of aneuploidy and meiotically based infertility.