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- Title
X-linked Inhibitor of Apoptosis Protein negatively regulates neuronal differentiation through interaction with cRAF and Trk.
- Authors
Fado, Rut; Moubarak, Rana S.; Miñano-Molina, Alfredo J.; Barneda-Zahonero, Bruna; Valero, Jorge; Saura, Carlos A.; Moran, Julio; Comella, Joan X.; Rodríguez-Álvarez, José
- Abstract
X-linked Inhibitor of apoptosis protein (XIAP) has been classically identified as a cell death regulator. Here, we demonstrate a novel function of XIAP as a regulator of neurite outgrowth in neuronal cells. In PC12 cells, XIAP overexpression prevents NGF-induced neuronal differentiation, whereas NGF treatment induces a reduction of endogenous XIAP levels concomitant with the induction of neuronal differentiation. Accordingly, downregulation of endogenous XIAP protein levels strongly increases neurite outgrowth in PC12 cells as well as axonal and dendritic length in primary cortical neurons. The effects of XIAP are mediated by the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERKs) pathway since blocking this pathway completely prevents the neuritogenesis mediated by XIAP downregulation. In addition, we found that XIAP binds to cRaf and Trk receptors. Our results demonstrate that XIAP plays a new role as a negative regulator of neurotrophin-induced neurite outgrowth and neuronal differentiation in developing neurons.
- Subjects
APOPTOSIS; CELL death; NERVOUS system; PHOSPHOTRANSFERASES; PROTEIN kinases
- Publication
Scientific Reports, 2013, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep02397