Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, China.
FASEB J. 2024 Sep 30;38(18):e70049. doi: 10.1096/fj.202400966R.
In this study, we have explored the role of the KATNB1 gene, a microtubule-severing protein, in the seminiferous epithelium of the rat testis. Our data have shown that KATNB1 expressed in rat brain, testes, and Sertoli cells. KATNB1 was found to co-localize with α-tubulin showing a unique stage-specific distribution across the seminiferous epithelium. Knockdown of KATNB1 by RNAi led to significant disruption of the tight junction (TJ) permeability barrier function in primary Sertoli cells cultured in vitro with an established functional TJ-barrier, as well as perturbations in the microtubule and actin cytoskeleton organization. The disruption in these cytoskeletal structures, in turn, led to improper distribution of TJ and basal ES proteins essential for maintaining the Sertoli TJ function. More importantly, overexpression of KATNB1 in the testis in vivo was found to block cadmium-induced blood-testis barrier (BTB) disruption and testis injury. KATNB1 exerted its promoting effects on BTB and spermatogenesis through corrective spatiotemporal expression of actin- and microtubule-based regulatory proteins by maintaining the proper organization of cytoskeletons in the testis, illustrating its plausible therapeutic implication. In summary, Katanin regulatory subunit B1 (KATNB1) plays a crucial role in BTB and spermatogenesis through its effects on the actin- and microtubule-based cytoskeletons in Sertoli cells and testis, providing important insights into male reproductive biology.
在这项研究中,我们探讨了 KATNB1 基因(一种微管切割蛋白)在大鼠睾丸生精上皮中的作用。我们的数据表明,KATNB1 在大鼠脑、睾丸和支持细胞中表达。KATNB1 与微管蛋白 α 共定位,在生精上皮中呈现独特的阶段性分布。用 RNAi 敲低 KATNB1 会导致体外培养的原代支持细胞紧密连接(TJ)通透性屏障功能显著破坏,TJ 和基底 ES 蛋白的微管和肌动蛋白细胞骨架组织发生紊乱。这些细胞骨架结构的紊乱反过来导致 TJ 和基底 ES 蛋白的分布不当,这些蛋白对维持支持细胞 TJ 功能至关重要。更重要的是,体内过表达 KATNB1 被发现可阻止镉诱导的血睾屏障(BTB)破坏和睾丸损伤。KATNB1 通过维持睾丸中细胞骨架的适当组织,对 actin 和微管为基础的调节蛋白进行正确的时空表达,对 BTB 和精子发生发挥促进作用,说明了其合理的治疗意义。总之,Katanin 调节亚基 B1(KATNB1)通过对支持细胞和睾丸中 actin 和微管为基础的细胞骨架的作用,在 BTB 和精子发生中发挥关键作用,为男性生殖生物学提供了重要的见解。