Non-classical testosterone signaling in spermatogenic GC-2 cells is mediated through ZIP9 interacting with Gnα11
| Autor: | Georgios Scheiner-Bobis, Lutz Konrad, Kai-Hui Chan, Mazen Shihan |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Biology Cell Line Mice Mediator Internal medicine Protein Interaction Mapping medicine Animals Testosterone Phosphorylation Receptor Cyclic AMP Response Element-Binding Protein Extracellular Signal-Regulated MAP Kinases Spermatogenesis Transcription factor G protein-coupled receptor Activating Transcription Factor 1 Spermatogenic Cell Cell Biology GTP-Binding Protein alpha Subunits Androgen receptor Endocrinology Receptors Androgen Signal transduction Protein Processing Post-Translational Protein Binding |
| Zdroj: | Cellular signalling. 27(10) |
| ISSN: | 1873-3913 |
| Popis: | 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 Gnα11. 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/Gnα11 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. |
| Databáze: | OpenAIRE |
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