Department of Cell and Developmental Biology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
Biochem J. 2013 May 15;452(1):67-78. doi: 10.1042/BJ20121006.
The NXF (nuclear export factor) family members are implicated in the transport of mRNA from the nucleus to the cytoplasm. Recently, some members of the NXF family have been reported to play divergent functional roles, such as post-transcriptional regulation, translational control, regulation of mRNA stability and trafficking. However, little is known about the roles of NXF3 in spermatogenesis. In the present study, we found that mouse NXF3, specifically expressed in principal cells in segment II of the caput epididymis, as well as Sertoli cells in the mouse testis, was required to mediate TGF-β (transforming growth factor β)-induced down-regulation of Tgfb3/TGF-β3 mRNA expression and protein secretion in Sertoli cells. In addition, NXF3 was also involved in TGF-β-induced transcriptional regulation of other genes associated with Sertoli cell maturation and the restructuring of the Sertoli cell BTB (blood-testis barrier), such as Gata1 (GATA-binding protein 1), Wt1 (Wilms's tumour homologue 1), Cldn11 (claudin11) and Cdkn1a (cyclin-dependent kinase inhibitor 1A or p21(Cip1)). The transcriptional regulation of NXF3 was mediated through physical interaction with STRAP (serine/threonine kinase receptor-associated protein), where NXF3 inhibited the complex formation among Smad7, STRAP and activated type I TGF-β receptor. Taken together, our data provide mechanistic insights into the roles of NXF3 in TGF-β-mediated expression of Tgfb3 and other genes. NXF3 may be implicated in Sertoli cell maturation and the extensive restructuring of the Sertoli cell BTB.
NXF（核输出因子）家族成员参与 mRNA 从细胞核到细胞质的运输。最近，一些 NXF 家族成员被报道具有不同的功能作用，如转录后调控、翻译控制、mRNA 稳定性和运输调节。然而，NXF3 在精子发生中的作用知之甚少。在本研究中，我们发现，小鼠 NXF3 特异性表达于附睾头部Ⅱ段主细胞以及睾丸中的支持细胞，介导 TGF-β（转化生长因子β）诱导的支持细胞中 Tgfb3/TGF-β3 mRNA 表达和蛋白分泌的下调。此外，NXF3 还参与 TGF-β 诱导的与支持细胞成熟和支持细胞 BTB（血睾屏障）重构相关的其他基因的转录调节，如 Gata1（GATA 结合蛋白 1）、Wt1（Wilms 瘤同源物 1）、Cldn11（claudin11）和 Cdkn1a（细胞周期蛋白依赖性激酶抑制剂 1A 或 p21(Cip1))。NXF3 的转录调节是通过与 STRAP（丝氨酸/苏氨酸激酶受体相关蛋白）的物理相互作用介导的，其中 NXF3 抑制了 Smad7、STRAP 和激活型 I TGF-β 受体之间的复合物形成。总之，我们的数据提供了 NXF3 在 TGF-β 介导的 Tgfb3 和其他基因表达中的作用的机制见解。NXF3 可能参与支持细胞成熟和支持细胞 BTB 的广泛重构。
