Konno Alu, Ikegami Koji, Konishi Yoshiyuki, Yang Hyun-Jeong, Abe Manabu, Yamazaki Maya, Sakimura Kenji, Yao Ikuko, Shiba Kogiku, Inaba Kazuo, Setou Mitsutoshi
Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 4313192, Japan Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 4313192, Japan.
Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 4313192, Japan International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 4313192, Japan.
J Cell Sci. 2016 Jul 15;129(14):2757-66. doi: 10.1242/jcs.185983. Epub 2016 Jun 2.
Nine outer doublet microtubules in axonemes of flagella and cilia are heterogeneous in structure and biochemical properties. In mammalian sperm flagella, one of the factors to generate the heterogeneity is tubulin polyglutamylation, although the importance of the heterogeneous modification is unclear. Here, we show that a tubulin polyglutamylase Ttll9 deficiency (Ttll9(-/-)) causes a unique set of phenotypes related to doublet heterogeneity. Ttll9(-/-) sperm axonemes had frequent loss of a doublet and reduced polyglutamylation. Intriguingly, the doublet loss selectively occurred at the distal region of doublet 7, and reduced polyglutamylation was observed preferentially on doublet 5. Ttll9(-/-) spermatozoa showed aberrant flagellar beating, characterized by frequent stalls after anti-hook bending. This abnormal motility could be attributed to the reduction of polyglutamylation on doublet 5, which probably occurred at a position involved in the switching of bending. These results indicate that mammalian Ttll9 plays essential roles in maintaining the normal structure and beating pattern of sperm flagella by establishing normal heterogeneous polyglutamylation patterns.
鞭毛和纤毛轴丝中的九条外周双联微管在结构和生化特性上是异质的。在哺乳动物精子鞭毛中,生成这种异质性的因素之一是微管蛋白多聚谷氨酰胺化,尽管这种异质修饰的重要性尚不清楚。在此,我们表明微管蛋白多聚谷氨酰胺酶Ttll9缺陷(Ttll9(-/-))会导致一组与双联微管异质性相关的独特表型。Ttll9(-/-)精子轴丝经常出现双联微管缺失且多聚谷氨酰胺化减少。有趣的是,双联微管缺失选择性地发生在双联微管7的远端区域,并且在双联微管5上优先观察到多聚谷氨酰胺化减少。Ttll9(-/-)精子表现出异常的鞭毛摆动,其特征是在反钩弯曲后频繁停顿。这种异常运动可能归因于双联微管5上多聚谷氨酰胺化的减少,这可能发生在与弯曲转换有关的位置。这些结果表明,哺乳动物Ttll9通过建立正常的异质多聚谷氨酰胺化模式,在维持精子鞭毛的正常结构和摆动模式中发挥着重要作用。