title: Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, II University of Naples, 80138 Naples, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Di Donato
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, II University of Naples, 80138 Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bilancio
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, II University of Naples, 80138 Naples, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: D'Amato
authors.affiliation: Telethon Institute of Genetics and Medicine and Medical Genetics and Translational Medicine Department, University Federico II, 80131 Naples, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Claudiani
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, II University of Naples, 80138 Naples, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Oliviero
authors.affiliation: European Laboratory for the Investigation of Food Induced Diseases and Medical Genetics and Translational Medicine Department, University Federico II, 80131 Naples, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Barone
authors.affiliation: Telethon Institute of Genetics and Medicine and Medical Genetics and Translational Medicine Department, University Federico II, 80131 Naples, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Auricchio
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892-4256.
authors.forename: Ettore
authors.initials: E
authors.lastname: Appella
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, II University of Naples, 80138 Naples, Italy antimo.migliaccio@unina2.it.
authors.forename: Antimo
authors.initials: A
authors.lastname: Migliaccio
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, II University of Naples, 80138 Naples, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Auricchio
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, II University of Naples, 80138 Naples, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Castoria
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D064448:Filamins / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D020932:Nerve Growth Factor / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D020239:Receptor Cross-Talk; D020917:Receptor, trkA / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: D064448:Filamins; D019012:Integrin beta1; D011944:Receptors, Androgen; D020932:Nerve Growth Factor; D020917:Receptor, trkA