Open AccessCross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells
Author(s) -
Marzia Di Donato,
Antonio Bilancio,
Loredana D’Amato,
Pamela Claudiani,
Maria Oliviero,
Maria Vittoria Barone,
Alberto Auricchio,
Ettore Appella,
Antimo Migliaccio,
Ferdinando Auricchio,
Gabriella Castoria
Publication year - 2015
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e14-09-1352
Subject(s) - tropomyosin receptor kinase a , androgen receptor , neurite , flna , biology , filamin , nerve growth factor , androgen , microbiology and biotechnology , receptor , signal transduction , endocrinology , medicine , low affinity nerve growth factor receptor , hormone , cell , biochemistry , in vitro , cytoskeleton , genetics , prostate cancer , cancer
Steroids and growth factors control neuronal development through their receptors under physiological and pathological conditions. We show that PC12 cells harbor endogenous androgen receptor (AR), whose inhibition or silencing strongly interferes with neuritogenesis stimulated by the nonaromatizable synthetic androgen R1881 or NGF. This implies a role for AR not only in androgen signaling, but also in NGF signaling. In turn, a pharmacological TrkA inhibitor interferes with NGF- or androgen-induced neuritogenesis. In addition, 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. This study thus 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 description of AR function in PC12 cells.