期刊
CELLULAR SIGNALLING
卷 27, 期 10, 页码 2077-2086出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2015.07.013
关键词
Testosterone; GPCR; ZIP9; Gn alpha 11; Androgen receptor
类别
资金
- German Research Foundation (DFG) [SCHE 307/7-1]
- Deutsche Forschungsgemeinschaft (DFG) [GRK 1871/1]
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 Zn2+ 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 Gn alpha 11. 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/Gn alpha 11 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. (C) 2015 Elsevier Inc. All rights reserved.
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