Premium
Bex1, a novel interactor of the p75 neurotrophin receptor, links neurotrophin signaling to the cell cycle
Author(s) -
Vilar Marçal,
MurilloCarretero Maribel,
Mira Helena,
Magnusson Kalle,
Besset Valerie,
Ibáñez Carlos F
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601017
Subject(s) - interactor , biology , neurotrophin , low affinity nerve growth factor receptor , microbiology and biotechnology , receptor , signal transduction , neurotrophin 3 , neuroscience , genetics , neurotrophic factors , brain derived neurotrophic factor
A screening for intracellular interactors of the p75 neurotrophin receptor (p75 NTR ) identified brain‐expressed X‐linked 1 (Bex1), a small adaptor‐like protein of unknown function. Bex1 levels oscillated during the cell cycle, and preventing the normal cycling and downregulation of Bex1 in PC12 cells sustained cell proliferation under conditions of growth arrest, and inhibited neuronal differentiation in response to nerve growth factor (NGF). Neuronal differentiation of precursors isolated from the brain subventricular zone was also reduced by ectopic Bex1. In PC12 cells, Bex1 overexpression inhibited the induction of NF‐κB activity by NGF without affecting activation of Erk1/2 and AKT, while Bex1 knockdown accelerated neuronal differentiation and potentiated NF‐κB activity in response to NGF. Bex1 competed with RIP2 for binding to the p75 NTR intracellular domain, and elevating RIP2 levels restored the ability of cells overexpressing Bex1 to differentiate in response to NGF. Together, these data establish Bex1 as a novel link between neurotrophin signaling, the cell cycle, and neuronal differentiation, and suggest that Bex1 may function by coordinating internal cellular states with the ability of cells to respond to external signals.