TY - JOUR
T1 - Presence of androgen receptor variant in neuronal lipid rafts
AU - Garza-Contreras, Jo
AU - Duong, Phong
AU - Snyder, Brina D.
AU - Schreihofer, Derek A.
AU - Cunningham, Rebecca L.
N1 - Publisher Copyright:
© 2017 Garza-Contreras et al.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Fast, nongenomic androgen actions have been described in various cell types, including neurons. However, the receptor mediating this cell membrane–initiated rapid signaling remains unknown. This study found a putative androgen receptor splice variant in a dopaminergic N27 cell line and in several brain regions (substantia nigra pars compacta, entorhinal cortex, and hippocampus) from gonadally intact and gonadectomized (young and middle-aged) male rats. This putative splice variant protein has a molecular weight of 45 kDa and lacks an N-terminal domain, indicating it is homologous to the human AR45 splice variant. Interestingly, AR45 was highly expressed in all brain regions examined. In dopaminergic neurons, AR45 is localized to plasma membrane lipid rafts, a microdomain involved in cellular signaling. Further, AR45 protein interacts with membrane-associated G proteins Gαq and Gαo. Neither age nor hormone levels altered AR45 expression in dopaminergic neurons. These results provide the first evidence of AR45 protein expression in the brain, specifically plasma membrane lipid rafts. AR45 presence in lipid rafts indicates that it may function as a membrane androgen receptor to mediate fast, nongenomic androgen actions.
AB - Fast, nongenomic androgen actions have been described in various cell types, including neurons. However, the receptor mediating this cell membrane–initiated rapid signaling remains unknown. This study found a putative androgen receptor splice variant in a dopaminergic N27 cell line and in several brain regions (substantia nigra pars compacta, entorhinal cortex, and hippocampus) from gonadally intact and gonadectomized (young and middle-aged) male rats. This putative splice variant protein has a molecular weight of 45 kDa and lacks an N-terminal domain, indicating it is homologous to the human AR45 splice variant. Interestingly, AR45 was highly expressed in all brain regions examined. In dopaminergic neurons, AR45 is localized to plasma membrane lipid rafts, a microdomain involved in cellular signaling. Further, AR45 protein interacts with membrane-associated G proteins Gαq and Gαo. Neither age nor hormone levels altered AR45 expression in dopaminergic neurons. These results provide the first evidence of AR45 protein expression in the brain, specifically plasma membrane lipid rafts. AR45 presence in lipid rafts indicates that it may function as a membrane androgen receptor to mediate fast, nongenomic androgen actions.
KW - Androgen receptor
KW - Caveolin
KW - G proteins
KW - Lipid rafts
KW - Membrane
KW - Signaling
UR - http://www.scopus.com/inward/record.url?scp=85032158014&partnerID=8YFLogxK
U2 - 10.1523/ENEURO.0109-17.2017
DO - 10.1523/ENEURO.0109-17.2017
M3 - Article
C2 - 28856243
AN - SCOPUS:85032158014
VL - 4
JO - eNeuro
JF - eNeuro
SN - 2373-2822
IS - 4
M1 - e0109-17.2017
ER -