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Full length TrkB potentiates estrogen receptor alpha mediated transcription suggesting convergence of susceptibility pathways in schizophrenia

journal contribution
posted on 2024-11-16, 07:43 authored by Jenny Wong, H G Woon, Cynthia Shannon Weickert
In this study, we determined if estrogen receptor alpha (ERα) can interact with the full length tropomyosin receptor kinase B (TrkB-TK+), both of which are implicated in schizophrenia pathogenesis. Using neuronal (SHSY5Y) and non-neuronal (CHOK1) cell-lines, we showed that TrkB-TK+ can increase transcription at estrogen response elements (EREs) with and without exogenous estrogen treatment. In the presence of estrogen, TrkB-TK+ further potentiated the effect of estrogen stimulation on ERα-mediated transcription. This synergistic effect of TrkB-TK+ on ERα-mediated transcription was not due to direct effects of TrkB-TK+ in the nucleus, but occurred through cytoplasmic signaling of TrkB-TK+ via the MAPK/ERK pathway to phosphorylate ERα, leading to an induction in ERα-mediated transcription. When we examined the PI3K/AKT pathway, we found that PI3K/AKT activity constitutively inhibited baseline transcription at EREs. Furthermore, we showed that signaling via PI3K/AKT inhibited TrkB-TK+-dependent transcriptional potentiation at EREs. Our findings suggest that TrkB-TK+-linked second messenger signaling pathways can reciprocally regulate ERα-mediated transcription at EREs. Considering that both ERα and TrkB-TK+ expression are reduced in schizophrenia, our findings suggest that dysfunction in TrkB-TK+ signaling may occur upstream of, or in conjunction with a dysfunction in ERα, and that transcriptional regulation by ERα may be decreased by reductions in TrkB-TK+. © 2010.

Funding

EVIDENCE OF (SELF)TRAINING OF WORKERS IN THE PRESS: AFFECTING THE SENSES, PRODUCING SENSITIVITIES (between the final decades of the 19th century and the beginning of the 21st century)

Coordenação de Aperfeicoamento de Pessoal de Nível Superior

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History

Citation

Wong, J., Woon, H. & Shannon Weickert, C. (2011). Full length TrkB potentiates estrogen receptor alpha mediated transcription suggesting convergence of susceptibility pathways in schizophrenia. Molecular and Cellular Neuroscience, 46 (1), 67-78.

Journal title

Molecular and cellular neurosciences

Volume

46

Issue

1

Pagination

67-78

Language

English

RIS ID

39149

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