PCP protein inversin regulates testis function through changes in cytoskeletal organization of actin and microtubules

Endocrinology. 2022 Feb 1:bqac009. doi: 10.1210/endocr/bqac009. Online ahead of print.ABSTRACTInversin is an integrated component of the Frizzled (Fzd)/Dishevelled (Dvl)/Diversin planar cell polarity (PCP) complex that is known to work in concert with the Van Gogh-like protein (e.g., Vangl2)/Prickle PCP complex to support tissue and organ development including the brain, kidney, pancreas and others. However, with the exception of Dvl3 and Vangl2, other PCP proteins have not been investigated in the testis. Herein, we used the technique of RNAi to examine the role of inversin (Invs) in Sertoli cell and testis function by corresponding studies in vitro and in vivo. When inversin was silenced by RNAi using specific siRNA duplexes by transfecting primary cultures of Sertoli cells in vitro or testes in vivo, it was shown that inversin knockdown (KD) perturbed the Sertoli cell tight junction (TJ)-barrier function in vitro and in vivo using corresponding physiological and integrity assays. More important, inversin exerted its regulatory effects through changes in the organization of the actin and microtubule (MT) cytoskeletons, including reducing the ability of their polymerization. These changes, in turn, induced defects in spermatogenesis due to loss of spermatid polarity, disruptive distribution of blood-testis barrier (BTB)-associated proteins at the Sertoli cell-cell interface, appearance of multi-nucleated round spermatids, and defects in the release of sperm at spermiation.PM...
Source: Endocrinology - Category: Endocrinology Authors: Source Type: research