Transcriptional co-activator YAP regulates cAMP signaling in Sertoli cells

- YAP is localized in the nucleus of cultured Sc.
- YAP inhibitor verteporfin down regulates cyclic AMP responsive genes in Sc.
- Verteporfin attenuates forskolin mediated up regulation of cyclic AMP responsive genes.
- YAP inhibition induces CREB phosphorylation at Ser 133 residue.
- Verteporfin induced CREB phosphorylation is attenuated in the presence of H89.

FSH mediated cyclic AMP (cAMP) signaling is crucial for function of testicular Sertoli cells (Sc) during puberty. Yes-kinase Associated Protein (YAP), a transcriptional co-activator, regulates cell proliferation and differentiation. However, its role in testicular function is not known. In present study, we have identified YAP as an important regulator of cAMP signaling in Sc, in-vitro. Verteporfin, a YAP-inhibitor, down regulated the expression of cAMP responsive genes necessary for spermatogenesis in Sc. Action of forskolin, which acts via cAMP, was also antagonized by verteporfin, limiting expression of these genes. Assessment of cAMP-responsive-element-binding-protein (CREB) phosphorylation revealed that verteporfin augmented the phosphorylation of CREB at Ser133 residue. This effect of verteporfin on CREB phosphorylation was attenuated by H-89, the PKA inhibitor. This clearly suggested involvement of PKA in verteporfin mediated CREB phosphorylation. We provided evidence for the first time that YAP modulates cAMP signaling in Sc which may be critical for testicular function.