Research Paper Volume 11, Issue 8 pp 2281—2294
Non-genomic mechanisms mediate androgen-induced PSD95 expression
- 1 Department of Anatomy, Hebei Medical University, Shijiazhuang, China
- 2 Neuroscience Research Center, Hebei Medical University, Shijiazhuang, China
- 3 Grade 2016, Clinical Medicine Specialty, Hebei Medical University, Shijiazhuang, China
- 4 Neurology Department, The Second Hospital of Hebei Medical University, Shijiazhuang, China
received: January 28, 2019 ; accepted: April 10, 2019 ; published: April 20, 2019 ;https://doi.org/10.18632/aging.101913
How to Cite
Copyright: Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The non-genomic actions of androgen-induced synaptic plasticity have been extensively studied. However, the underlying mechanisms remain controversial. We recently found that testosterone-fetal bovine serum albumin (T-BSA), a cell membrane-impermeable complex, led to a rapid increase in the postsynaptic density 95 (PSD95) protein level through a transcription-independent mechanism in mouse hippocampal HT22 cells. Using T-BSA conjugated FITC, we verified the presence of membrane androgen-binding sites. Here, we show that T-BSA-induced PSD95 expression is mediated by G-protein-coupled receptor (GPCR)-zinc transporter ZIP9 (SLC39A9), one of the androgen membrane binding sites, rather than the membrane-localized androgen receptor. Furthermore, we found that T-BSA induced an interaction between ZIP9 and Gnα11 that lead to the phosphorylation of Erk1/2 MAPK and eIF4E, which are critical in the mRNA translation process. The PSD95 and p-eIF4E expression decreased when knockdown of ZIP9 or Gnα11 expression or inhibition of Erk1/2 activation. Taken together, these findings suggest that ZIP9 mediates the non-genomic action of androgen on synaptic protein PSD95 synthesis through the Gnα11/Erk1/2/eIF4E pathway in HT22 cells. This novel mechanism provides a theoretical basis to understand the neuroprotective mechanism of androgen.