Non-genomic mechanisms mediate androgen-induced PSD95 expression.
Aging (Albany NY)
; 11(8): 2281-2294, 2019 04 20.
Article
em En
| MEDLINE
| ID: mdl-31005955
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Testosterona
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Soroalbumina Bovina
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Receptores Androgênicos
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Proteínas de Transporte de Cátions
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Proteína 4 Homóloga a Disks-Large
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Hipocampo
Limite:
Animals
Idioma:
En
Revista:
Aging (Albany NY)
Ano de publicação:
2019
Tipo de documento:
Article