近日，法国巴黎文理研究大学Carsten Janke等研究人员合作发现，微管蛋白糖基化调控轴丝动力蛋白活性、鞭毛游动以及雄性生育能力。相关论文于2021年1月8日发表在《科学》杂志上。

研究人员生成了完全缺乏微管蛋白糖基化的小鼠模型。雄性小鼠由于其精子鞭毛的异常游动模式（这阻碍了精子细胞的正常游动）而不能生育。使用冷冻电子断层扫描，研究人员发现缺乏糖基化会导致精子轴丝内的动力蛋白臂异常构象，从而为观察到的功能障碍提供了结构基础。这些发现揭示了微管糖基化对于控制鞭毛游动、定向精子游泳和男性生育的重要性。

据悉，微管细胞骨架的翻译后修饰已成为细胞功能的关键调节因素，其干扰已与越来越多的人类病理学联系在一起。微管蛋白糖基化特异性地修饰纤毛和鞭毛中的微管，但其功能和机制作用仍不清楚。

附：英文原文

Title: Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility

Author: Sudarshan Gadadhar, Gonzalo Alvarez Viar, Jan Niklas Hansen, An Gong, Aleksandr Kostarev, Cme Ialy-Radio, Sophie Leboucher, Marjorie Whitfield, Ahmed Ziyyat, Aminata Touré, Luis Alvarez, Gaia Pigino, Carsten Janke

Issue&Volume: 2021/01/08

Abstract: Posttranslational modifications of the microtubule cytoskeleton have emerged as key regulators of cellular functions, and their perturbations have been linked to a growing number of human pathologies. Tubulin glycylation modifies microtubules specifically in cilia and flagella, but its functional and mechanistic roles remain unclear. In this study, we generated a mouse model entirely lacking tubulin glycylation. Male mice were subfertile owing to aberrant beat patterns of their sperm flagella, which impeded the straight swimming of sperm cells. Using cryo–electron tomography, we showed that lack of glycylation caused abnormal conformations of the dynein arms within sperm axonemes, providing the structural basis for the observed dysfunction. Our findings reveal the importance of microtubule glycylation for controlled flagellar beating, directional sperm swimming, and male fertility.

DOI: 10.1126/science.abd4914

Source: https://science.sciencemag.org/content/371/6525/eabd4914