Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Department of Biochemistry, The School of Molecular and Cellular Biology, College of Liberal Arts & Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Nucleic Acids Res. 2024 Nov 11;52(20):12244-12261. doi: 10.1093/nar/gkae862.
Spermatogenesis is a biological process within the testis that produces haploid spermatozoa for the continuity of species. Sertoli cells are somatic cells in the seminiferous epithelium that orchestrate spermatogenesis. Cyclic reorganization of the Sertoli cell actin cytoskeleton is vital for spermatogenesis, but the underlying mechanism remains largely unclear. Here, we report that the RNA-binding protein PTBP1 controls Sertoli cell actin cytoskeleton reorganization by programming alternative splicing of actin cytoskeleton regulators. This splicing control enables ectoplasmic specializations, the actin-based adhesion junctions, to maintain the blood-testis barrier and support spermatid transport and transformation. Particularly, we show that PTBP1 promotes actin bundle formation by repressing the inclusion of exon 14 of Tnik, a kinase present at the ectoplasmic specialization. Our results thus reveal a novel mechanism wherein Sertoli cell actin cytoskeleton dynamics are controlled post-transcriptionally by utilizing functionally distinct isoforms of actin regulatory proteins, and PTBP1 is a critical regulatory factor in generating such isoforms.
精子发生是睾丸内的一个生物学过程，它产生用于物种延续的单倍体精子。支持细胞是生精上皮中的体细胞，它们协调精子发生。支持细胞肌动蛋白细胞骨架的周期性重排对于精子发生至关重要，但潜在的机制在很大程度上仍不清楚。在这里，我们报告 RNA 结合蛋白 PTBP1 通过编程肌动蛋白细胞骨架调节剂的选择性剪接来控制支持细胞肌动蛋白细胞骨架的重排。这种剪接控制使胞质特殊化，即基于肌动蛋白的黏附连接，能够维持血睾屏障并支持精子变形和运输。具体来说，我们表明，PTBP1 通过抑制位于胞质特殊化部位的激酶 Tnik 的外显子 14 的包含，促进肌动蛋白束的形成。因此，我们的结果揭示了一种新的机制，即支持细胞肌动蛋白细胞骨架动力学通过利用肌动蛋白调节蛋白的功能不同的异构体进行转录后控制，并且 PTBP1 是产生这种异构体的关键调节因子。
