PA1 participates in the maintenance of blood-testis barrier integrity via cooperation with JUN in the Sertoli cells of mice.
PA1 participates in the maintenance of blood-testis barrier integrity via cooperation with JUN in the Sertoli cells of mice.
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PA1 通过与小鼠支持细胞中的 JUN 合作参与维持血睾屏障完整性
DOI：
10.1186/s13578-022-00773-y
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发表时间：
2022-04-04
影响因子：
7.5
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Liu B;Liu C;Ma B;Zhang R;Zhao Z;Xiao S;Cao W;Ma Y;Zhu G;Li W;Li Z
血睾屏障（BTB）是精子发生的重要微环境，支持细胞是血睾屏障的细胞基础。许多核转录因子已被确定为支持细胞的正常功能至关重要。PA 1在多种生物学过程中发挥重要作用，但其在雄性生殖中的潜在功能尚不清楚。在这里，我们发现，PA 1是高度表达的人类和小鼠睾丸，主要定位于支持细胞的细胞核。Sertoli细胞特异性Pa 1基因敲除导致小鼠无精子症样表型。该基因的敲除导致精子发生中的多种缺陷，例如基底和顶端外质特化期间细胞骨架的解体以及BTB的破坏。进一步的转录组学分析，以及在支持细胞中的PA 1的Cut-Tag结果，揭示了PA 1可以影响支持细胞的正常功能所必需的基因子集的表达，包括与肌动蛋白组织和细胞连接相关的那些基因，如连接蛋白43（Cx43）。我们进一步证明Cx43的表达取决于AP-1复合转录因子之一JUN与PA 1之间的相互作用。总的来说，我们的研究结果表明，PA 1是必不可少的维持BTB的完整性在支持细胞和调节BTB的建设相关的基因表达通过转录因子。因此，这一新发现的机制在支持细胞提供了一个潜在的诊断，甚至治疗目标的一些个人与无精子症。在线版本包含补充材料，可通过10.1186/s13578-022-00773-y获得。
The blood–testis barrier (BTB) is essential to the microenvironment of spermatogenesis, and Sertoli cells provide the cellular basis for BTB construction. Numerous nuclear transcription factors have been identified to be vital for the proper functioning of Sertoli cells. PA1 has been reported to play important roles during diverse biological processes, yet its potential function in male reproduction is still unknown. Here, we show that PA1 was highly expressed in human and mouse testis and predominantly localized in the nuclei of Sertoli cells. Sertoli cell-specific Pa1 knockout resulted in an azoospermia-like phenotype in mice. The knockout of this gene led to multiple defects in spermatogenesis, such as the disorganization of the cytoskeleton during basal and apical ectoplasmic specialization and the disruption of the BTB. Further transcriptomic analysis, together with Cut-Tag results of PA1 in Sertoli cells, revealed that PA1 could affect the expression of a subset of genes that are essential for the normal function of Sertoli cells, including those genes associated with actin organization and cellular junctions such as Connexin43 (Cx43). We further demonstrated that the expression of Cx43 depended on the interaction between JUN, one of the AP-1 complex transcription factors, and PA1. Overall, our findings reveal that PA1 is essential for the maintenance of BTB integrity in Sertoli cells and regulates BTB construction-related gene expression via transcription factors. Thus, this newly discovered mechanism in Sertoli cells provides a potential diagnostic or even therapeutic target for some individuals with azoospermia. The online version contains supplementary material available at 10.1186/s13578-022-00773-y.
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DOI：
10.1083/jcb.201205025
发表时间：
2012-07-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fontana X;Hristova M;Da Costa C;Patodia S;Thei L;Makwana M;Spencer-Dene B;Latouche M;Mirsky R;Jessen KR;Klein R;Raivich G;Behrens A
通讯作者：
Behrens A
影响因子：
7.2
作者：
Daneman, Richard;Prat, Alexandre
通讯作者：
Prat, Alexandre
影响因子：
3.5
作者：
Ghouili, Firas;Martin, Luc J.
通讯作者：
Martin, Luc J.
影响因子：
17.1
作者：
Griffin MF;Borrelli MR;Garcia JT;Januszyk M;King M;Lerbs T;Cui L;Moore AL;Shen AH;Mascharak S;Diaz Deleon NM;Adem S;Taylor WL;desJardins-Park HE;Gastou M;Patel RA;Duoto BA;Sokol J;Wei Y;Foster D;Chen K;Wan DC;Gurtner GC;Lorenz HP;Chang HY;Wernig G;Longaker MT
通讯作者：
Longaker MT
DOI：
10.1007/978-1-4939-7698-0_17
发表时间：
2018
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Chen H;Lui WY;Mruk DD;Xiao X;Ge R;Lian Q;Lee WM;Silvestrini B;Cheng CY
通讯作者：
Cheng CY