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.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Di Donato M,Bilancio A,D'Amato L,Claudiani P,Oliviero MA,Barone MV,Auricchio A,Appella E,Migliaccio A,Auricchio F,Castoria Gdoi
10.1091/mbc.E14-09-1352subject
Has Abstractpub_date
2015-08-01 00:00:00pages
2858-72issue
15eissn
1059-1524issn
1939-4586pii
mbc.E14-09-1352journal_volume
26pub_type
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