Steroids and growth factors control neuronal development through their receptors under physiological and pathological conditions. We here report that PC12 cells harbor endogenous androgen receptor (AR), whose inhibition or silencing strongly interferes in neuritogenesis stimulated by the non-aromatizable synthetic androgen R1881 or NGF. This implies a role for AR not only in androgen, but also in NGF signaling. In turn, a pharmacological TrkA inhibitor interferes in NGF- or androgen-induced neuritogenesis. Additionally, androgen or NGF triggers AR association with TrkA, TrkA interaction with PI3-K δ and downstream activation of PI3-K δ and Rac in PC12 cells. Once associated with AR, filamin A (FlnA) contributes to androgen or NGF neuritogenesis, likely through its interaction with signaling effectors, such as Rac. Our study identifies a previously unrecognized reciprocal cross talk between AR and TrkA, which is controlled by β1 integrin. The contribution of FlnA/AR complex and PI3-K δ to neuronal differentiation by androgens and NGF is also novel. This is the first report to describe AR function in PC12 cells.

CROSS TALK BETWEEN ANDROGEN RECEPTOR/ FILAMIN A AND TrkA REGULATES NEURITE OUTGROWTH IN PC12 CELLS

Marzia Di Donato;BILANCIO, Antonio;MIGLIACCIO, Antimo;CASTORIA, Gabriella
2016

Abstract

Steroids and growth factors control neuronal development through their receptors under physiological and pathological conditions. We here report that PC12 cells harbor endogenous androgen receptor (AR), whose inhibition or silencing strongly interferes in neuritogenesis stimulated by the non-aromatizable synthetic androgen R1881 or NGF. This implies a role for AR not only in androgen, but also in NGF signaling. In turn, a pharmacological TrkA inhibitor interferes in NGF- or androgen-induced neuritogenesis. Additionally, androgen or NGF triggers AR association with TrkA, TrkA interaction with PI3-K δ and downstream activation of PI3-K δ and Rac in PC12 cells. Once associated with AR, filamin A (FlnA) contributes to androgen or NGF neuritogenesis, likely through its interaction with signaling effectors, such as Rac. Our study identifies a previously unrecognized reciprocal cross talk between AR and TrkA, which is controlled by β1 integrin. The contribution of FlnA/AR complex and PI3-K δ to neuronal differentiation by androgens and NGF is also novel. This is the first report to describe AR function in PC12 cells.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11591/192713
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