School of Biological Sciences, Faculty of Science, Monash University, Clayton, VIC, 3800, Australia.
School of BioSciences, Faculty of Science, The University of Melbourne, Parkville, VIC, 3010, Australia.
Development. 2021 Dec 15;148(24). doi: 10.1242/dev.199922.
Katanin microtubule-severing enzymes are crucial executers of microtubule regulation. Here, we have created an allelic loss-of-function series of the katanin regulatory B-subunit KATNB1 in mice. We reveal that KATNB1 is the master regulator of all katanin enzymatic A-subunits during mammalian spermatogenesis, wherein it is required to maintain katanin A-subunit abundance. Our data shows that complete loss of KATNB1 from germ cells is incompatible with sperm production, and we reveal multiple new spermatogenesis functions for KATNB1, including essential roles in male meiosis, acrosome formation, sperm tail assembly, regulation of both the Sertoli and germ cell cytoskeletons during sperm nuclear remodelling, and maintenance of seminiferous epithelium integrity. Collectively, our findings reveal that katanins are able to differentially regulate almost all key microtubule-based structures during mammalian male germ cell development, through the complexing of one master controller, KATNB1, with a 'toolbox' of neofunctionalised katanin A-subunits.
卡坦丁微管切割酶是微管调节的关键执行者。在这里,我们在小鼠中创建了一系列等位基因缺失功能的卡坦丁调节 B 亚基 KATNB1。我们揭示了 KATNB1 是哺乳动物精子发生过程中所有卡坦丁 A 亚基的主要调节剂,在精子发生过程中需要维持卡坦丁 A 亚基的丰度。我们的数据表明,生殖细胞中完全缺失 KATNB1 与精子生成不相容,我们揭示了 KATNB1 的多个新的精子发生功能,包括在减数分裂、顶体形成、精子尾部组装、精子核重塑过程中调节生精细胞和精母细胞细胞骨架以及维持生精上皮完整性中的重要作用。总的来说,我们的研究结果表明,卡坦丁能够通过与“工具箱”中的一个主控制器 KATNB1 结合,调节一个主控制器 KATNB1,来调节哺乳动物雄性生殖细胞发育过程中几乎所有关键的基于微管的结构,从而实现新功能化的卡坦丁 A 亚基的差异化调节。