In cilia and flagella, dyneins form complexes which give rise to the inner and outer axonemal arms. Defects in the dynein arms are the leading cause of primary ciliary dyskinesia (PCD), which is characterized by chronic respiratory infections, situs inversus, and sterility. While the pathological features associated with PCD are increasingly well characterized, many of the causative genetic lesions remain elusive. Using Drosophila, here we analyze genetic requirements for wampa (wam), a previously uncharacterized component of the outer dynein arm. While homozygous mutant animals are viable and display no morphological defects, loss of wam results in complete male sterility. Ultrastructural analysis further reveals that wam mutant spermatids lack the axonemal outer dynein arms, which leads to a complete loss of flagellar motility. In addition to a role in outer dynein arm formation, we also uncover other novel microtubule-associated requirements for wam during spermatogenesis, including the regulation of mitochondrial localization and the shaping of the nuclear head. Due to the conserved nature of dyneins, this study advances our understanding of the pathology of PCD and the functional role of dyneins in axoneme formation and other aspects of spermatogenesis.

中文翻译：

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Wampa 是果蝇轴索组装和雄性生育力所需的动力蛋白亚基。

在纤毛和鞭毛中，动力蛋白形成复合物，产生内部和外部轴突臂。动力蛋白臂的缺陷是原发性纤毛运动障碍 (PCD) 的主要原因，PCD 的特点是慢性呼吸道感染、内翻位和不育。虽然与 PCD 相关的病理特征越来越得到很好的表征，但许多致病的遗传病变仍然难以捉摸。使用果蝇，我们在这里分析了 wampa (wam) 的遗传要求，wampa (wam) 是外动力蛋白臂的一种以前未表征的成分。虽然纯合突变动物可以存活并且没有形态缺陷，但 wam 的丧失会导致完全雄性不育。超微结构分析进一步表明 wam 突变精子细胞缺乏轴索外动力蛋白臂，这导致鞭毛运动完全丧失。除了在外动力蛋白臂形成中的作用外，我们还发现了精子发生过程中 wam 的其他新的微管相关要求，包括线粒体定位的调节和核头的形成。由于动力蛋白的保守性质，这项研究增进了我们对 PCD 病理学和动力蛋白在轴丝形成和精子发生其他方面的功能作用的理解。