Raptor directs Sertoli cell cytoskeletal organization and polarity in the mouse testis.
Raptor directs Sertoli cell cytoskeletal organization and polarity in the mouse testis.
复制标题
Raptor 指导小鼠睾丸中支持细胞的细胞骨架组织和极性。
DOI：
10.1093/biolre/ioy144
复制
发表时间：
2018
影响因子：
3.6
通讯作者：
Chen Zhenguo
中科院分区：
文献类型：
--
作者：
Xiong Zhi;Wang Caixia;Wang Zilong;Dai Huaiqian;Song Qiancheng;Zou Zhipeng;Xiao Bo;Zhao Allen Zijian;Bai Xiaochun;Chen Zhenguo
Sertoli cells (SCs) play a central role in testis development, and their normal number and functions are required for spermatogenesis. Although the canonical tuberous sclerosis complex–mammalian target of rapamycin complex 1(TSC-mTORC1) pathway is critical for testis development and spermatogenesis, the signaling mechanisms governing SC functions remain unclear. In this study, we generated two SC-specific mouse mutants using the Cre–LoxP system. Loss ofRaptor(a key component of mTORC1) caused severe tubular degeneration in the neonatal testis and adult mice displayed azoospermia, while adultRheb(an upstream activator for mTORC1) mutant mice had intact tubules and many sperm in their epididymides. Disruption of cytoskeletal organization, including actin, microtubules, and SC-intrinsic vimentin, was observed inRaptorbut notRhebmutant mice. We investigated the reasons for these different effects by whole-transcriptome sequencing, and found that expression of the tight junction adaptor protein cingulin was significantly reduced inRaptormutant mice. The expression profile of cingulin was synchronous with the differentiation and cytoskeletal dynamics of SCs in control mice, but was disordered inRaptormutant mice. Furthermore, activity of the small GTPase Rac1 was reduced and expression of the guanine exchange factor for Rac1, Asef, was decreased inRaptorbut notRhebmutant mice. Collectively, these findings establish novel functions of Raptor, independent of the canonical Rheb/mTORC1 pathway, in controlling cytoskeletal homeostasis and cell polarity in SCs, by affecting cingulin expression and Rac1 activity.
