AUTHOR=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 

TITLE=KISS1R and ANKRD31 Cooperate to Enhance Leydig Cell Gene Expression via the Cytoskeletal-Nucleoskeletal Pathway

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.877270

DOI=10.3389/fcell.2022.877270

ISSN=2296-634X

ABSTRACT=<p>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 <italic>via</italic> the cytoskeletal–nucleoskeletal pathway. Kp/KISS1R system deregulation, expression impairment of cytoskeletal–nucleoskeletal mediators, Leydig gene targets, and the decreased testosterone secretion in <italic>Ankrd31</italic><sup><italic>−/−</italic></sup> 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.</p>