| First Author | Shihan M | Year | 2015 |
| Journal | Cell Signal | Volume | 27 |
| Issue | 10 | Pages | 2077-86 |
| PubMed ID | 26208885 | Mgi Jnum | J:331912 |
| Mgi Id | MGI:6791231 | Doi | 10.1016/j.cellsig.2015.07.013 |
| Citation | Shihan M, et al. (2015) Non-classical testosterone signaling in spermatogenic GC-2 cells is mediated through ZIP9 interacting with Gnalpha11. Cell Signal 27(10):2077-86 |
| abstractText | Although classical and non-classical signaling of testosterone has been documented in several investigations, the nature of the receptor involved in the non-classical pathway remains a source of controversy. While some investigators favor the exclusive participation of the cytosolic/nuclear androgen receptor (AR) in both pathways, others propose a membrane-bound receptor as the mediator of the non-classical testosterone signaling. Evidence is provided here that in the spermatogenic cell line GC-2 the non-classical signaling pathway of testosterone, characterized through the activation of Erk1/2 and transcription factors like CREB or ATF-1, is not mediated through the classical nuclear androgen receptor (AR) but rather by a membrane-associated receptor. This receptor is ZIP9, a Zn(2+) transporter from the family of the ZRT, IRT-like proteins (ZRT=zinc-regulated transporter; IRT=iron-regulated transporter), which directly interacts with the G-protein Gnalpha11. siRNA-induced abrogation of the expression of either of these two proteins, whose close contacts are demonstrated by an in situ proximity assay, completely prevents all non-classical signaling effects of testosterone addressed. In contrast, silencing of AR expression does not influence the same signaling events. The identification of ZIP9/Gnalpha11 interactions as the mediators of the non-classical testosterone signaling cascade in spermatogenic GC-2 cells might help to supplement our knowledge concerning the role of testosterone in male fertility and reproduction. |
