1. Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells
- Author
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Loredana D'Amato, Gabriella Castoria, Ferdinando Auricchio, Maria Oliviero, Marzia Di Donato, A. Bilancio, Pamela Claudiani, Alberto Auricchio, Maria Vittoria Barone, Antimo Migliaccio, Ettore Appella, Di Donato, Marzia, Bilancio, Antonio, D'Amato, Loredana, Claudiani, Pamela, Oliviero, Maria Antoniett, Barone, Maria Vittoria, Auricchio, Alberto, Appella, Ettore, Migliaccio, Antimo, Auricchio, Ferdinando, Castoria, Gabriella, DI DONATO, Marzia, Loredana, D'Amato, Pamela, Claudiani, Maria Antonietta Oliviero, Maria Vittoria Barone, Alberto, Auricchio, Ettore, Appella, and Ferdinando, Auricchio
- Subjects
medicine.medical_specialty ,animal structures ,Neurite ,medicine.drug_class ,Filamins ,neurons ,Biology ,Tropomyosin receptor kinase A ,urologic and male genital diseases ,Filamin ,Models, Biological ,PC12 Cells ,Mice ,androgen receptor ,Internal medicine ,Nerve Growth Factor ,Neurites ,medicine ,Animals ,FLNA ,Receptor, trkA ,Receptor ,Molecular Biology ,Cells, Cultured ,TrkA ,Integrin beta1 ,Receptor Cross-Talk ,Articles ,Cell Biology ,Androgen ,Signaling ,Rats ,Cell biology ,Mice, Inbred C57BL ,Androgen receptor ,Endocrinology ,nervous system ,Receptors, Androgen - Abstract
Androgens stimulate neuronal differentiation of PC12 cells by nontranscriptional action of the endogenous androgen receptor (AR). AR is also required for NGF-induced neuritogenesis of PC12. Androgens or NGF trigger AR association with filamin and TrkA, TrkA interaction with PI3-K δ, and activation of PI3-K δ and Rac., 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.
- Published
- 2015