Photo Credit: JOSE LUIS CALVO MARTIN & JOSE ENRIQUE GARCIA-MAURIÑO MUZQUIZ

The following is a summary of “Planar Cell Polarity Protein Fat1 in Sertoli Cell Function,” published in the June 2024 issue of Endocrinology by Bu et al.

For a study, researchers sought to investigate the roles of Fat (FAT atypical cadherin) and Dchs (Dachsous cadherin–related protein) at different interfaces within the testicular structure, focusing on their intercellular adhesive functions supported by Fjx1, a nonreceptor Ser/Thr protein kinase. The research builds upon previous findings from Drosophila studies, aiming to elucidate the impact of Fat1 knockdown on Sertoli cell function and the integrity of the blood-testis barrier (BTB) in vitro.

Primary cultures of Sertoli cells, mimicking the BTB, were used to knock down Fat1 using RNA interference (RNAi). Functional assays were conducted to assess Sertoli cell tight junction (TJ) permeability and to evaluate TJ integrity in vitro. The study employed a series of experiments to monitor the modulation of actin and microtubule cytoskeletal dynamics by Fat1, specifically through its interaction with the Fat1/Fjx1 complex. Additionally, interactions of Fat1 with β-catenin, α-N-catenin, and Prickle 1 of the Vangl1/Prickle 1 complex were examined to understand their role in supporting intercellular interactions and maintaining planar cell polarity (PCP).

The findings revealed that Fat1 plays a pivotal role in Sertoli cell function by influencing actin and microtubule cytoskeletal dynamics, which is crucial for maintaining TJ permeability and integrity. Knockdown of Fat1 disrupted these functions, impairing the ability of Sertoli cells to form stable intercellular bridges essential for PCP. The study underscored the intricate association of Fat:Dchs and the Vangl2:Fzd PCP intercellular bridges with basal ES/TJ structural proteins, highlighting their critical role in stabilizing PCP function at critical Sertoli: Sertoli and Sertoli: spermatid interfaces during spermatogenesis.

In conclusion, the research underscored the essential role of Fat1 and its associated proteins in maintaining the structural integrity and function of the blood-testis barrier. The study provided insights into the mechanisms through which Fat1 influences cytoskeletal dynamics and intercellular adhesion, thereby contributing to the regulation of planar cell polarity critical for spermatogenesis. The findings contributed to the understanding of the molecular mechanisms underlying testicular function and may offer insights into potential therapeutic targets for male infertility and related disorders.

Reference: academic.oup.com/endo/article-abstract/165/6/bqae041/7637763