Ricci Giulia, Guillou Florian, Catizone Angela, Mele Vincenza Grazia, Moggio Martina, Chioccarelli Teresa, Diano Nadia, Meccariello Rosaria, Pierantoni Riccardo, Fasano Silvia, Cobellis Gilda, Chianese Rosanna, Manfrevola Francesco
Dipartimento di Medicina Sperimentale, Università degli Studi della Campania L. Vanvitelli, Naples, Italy.
CNRS, IFCE, INRAE, Université de Tours, PRC, Nouzilly, France.
Front Cell Dev Biol. 2022 Jun 23;10:877270. doi: 10.3389/fcell.2022.877270. eCollection 2022.
Kisspeptins are involved in the regulation of hypothalamic-pituitary-gonadal axis, Leydig cell functions, and testosterone secretion, acting as endogenous ligands of the KISS1 receptor. ANKRD31 protein participates in male fertility, regulating meiotic progression, and epididymal sperm maturation. Here, we show that in Leydig cells, KISS1 receptor and ANKRD31 proteins physically interact; the formation of this protein complex is enhanced by Kisspeptin-10 that also modulates F-actin synthesis, favoring histone acetylation in chromatin and gene expression the cytoskeletal-nucleoskeletal pathway. Kp/KISS1R system deregulation, expression impairment of cytoskeletal-nucleoskeletal mediators, Leydig gene targets, and the decreased testosterone secretion in testis strongly supported our hypothesis. Furthermore, cytochalasin D treatment subverted the gene expression induction dependent on Kisspeptin-10 action. In conclusion, the current work highlights a novel role for the Kisspeptin-10 in the induction of the cytoskeletal-nucleoskeletal route, downstream a physical interaction between KISS1 receptor and ANKRD31, with gene expression activation as final effect, in Leydig cells.
亲吻素参与下丘脑-垂体-性腺轴、睾丸间质细胞功能及睾酮分泌的调节，作为KISS1受体的内源性配体发挥作用。锚蛋白重复结构域蛋白31（ANKRD31）参与雄性生育，调节减数分裂进程及附睾精子成熟。在此，我们发现，在睾丸间质细胞中，KISS1受体与ANKRD31蛋白存在物理相互作用；亲吻素-10可增强该蛋白复合物的形成，其还可调节F-肌动蛋白合成，促进染色质中的组蛋白乙酰化及基因表达，即细胞骨架-核骨架途径。Kp/KISS1R系统失调、细胞骨架-核骨架介质表达受损、睾丸间质细胞基因靶点及睾丸中睾酮分泌减少有力地支持了我们的假设。此外，细胞松弛素D处理可颠覆依赖亲吻素-10作用的基因表达诱导。总之，目前的研究突出了亲吻素-10在诱导细胞骨架-核骨架途径中的新作用，该途径位于KISS1受体与ANKRD31的物理相互作用下游，最终效应是激活基因表达，发生在睾丸间质细胞中。
