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 - Funding Information:
Received March 27, 2017; accepted August 14, 2017; First published August 22, 2017. Authors report no conflicts of interest. Author contributions: JG-C and RLC designed the study; JG-C, PD, BDS, and DAS conducted the research; JG-C, DAS, and RLC analyzed the data; RLC wrote the paper. This study was funded by the National Institute of Neurological Disorders and Stroke (R01 NS088514) to RLC. Acknowledgments: We thank Drs. J. Thomas Cunningham, Robert Barber, and Robert Luedtke for their technical assistance.
Publisher Copyright:
© 2017 Garza-Contreras et al.
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
SN - 2373-2822
VL - 4
JO - eNeuro
JF - eNeuro
IS - 4
M1 - e0109-17.2017
ER -