Department of Biochemistry and Molecular Medicine, West Virginia University School of Medicine, Morgantown, WV, 26506, USA.
Department of Ophthalmology and Visual Sciences, West Virginia University School of Medicine, Morgantown, WV, 26506, USA.
Sci Rep. 2024 Sep 7;14(1):20889. doi: 10.1038/s41598-024-71303-8.
Microtubules, polymers of αβ-tubulin heterodimers, are essential for various cellular processes. The incorporation of different tubulin isotypes, each encoded by distinct genes, is proposed to contribute to the functional diversity observed in microtubules. However, the functional roles of each tubulin isotype are not completely understood. In this study, we investigated the role of the β4B-tubulin isotype (Tubb4b) in spermatogenesis, utilizing a Tubb4b knockout mouse model. We showed that β4B-tubulin is expressed in the germ cells throughout spermatogenesis. β4B-tubulin was localized to cytoplasmic microtubules, mitotic spindles, manchette, and axonemes of sperm flagella. We found that the absence of β4B-tubulin resulted in male infertility and failure to produce sperm cells. Our findings demonstrate that a lack of β4B-tubulin leads to defects in the initial stages of spermatogenesis. Specifically, β4B-tubulin is needed for the expansion of differentiating spermatogonia, which is essential for the subsequent progression of spermatogenesis.
微管是由αβ-微管蛋白异二聚体组成的聚合物,对于各种细胞过程都是必不可少的。不同的微管蛋白同工型的掺入,每种同工型都由不同的基因编码,被认为有助于微管中观察到的功能多样性。然而,每种微管蛋白同工型的功能作用尚不完全清楚。在这项研究中,我们利用 Tubb4b 敲除小鼠模型研究了β4B-微管蛋白同工型(Tubb4b)在精子发生中的作用。我们表明,β4B-微管蛋白在整个精子发生过程中存在于生殖细胞中。β4B-微管蛋白定位于细胞质微管、有丝分裂纺锤体、顶体囊和精子鞭毛的轴丝。我们发现,缺乏β4B-微管蛋白导致雄性不育和精子细胞无法产生。我们的研究结果表明,缺乏β4B-微管蛋白会导致精子发生的初始阶段出现缺陷。具体而言,β4B-微管蛋白对于分化精原细胞的扩张是必需的,这对于随后的精子发生进展至关重要。