X-linked Inhibitor of Apoptosis Protein negatively regulates neuronal differentiation through interaction with cRAF and Trk

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...

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Bibliographic Details
Authors: Fadó, Rut|||0000-0002-3293-2342, Moubarak, Rana S.|||0000-0003-2096-1258, Miñano Molina, Alfredo Jesús|||0000-0002-7761-5682, Barneda Zahonero, Bruna|||0000-0002-6557-5222, Valero Gomez-Lobo, Jorge, Saura Antolín, Carlos|||0000-0003-3692-5657, Morán, Julio, Comella i Carnicé, Joan Xavier|||0000-0002-6218-0786, Rodríguez Álvarez, José|||0000-0001-8582-8082
Format: article
Publication Date:2013
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:115507
Online Access:https://ddd.uab.cat/record/115507
https://dx.doi.org/urn:doi:10.1038/srep02397
Access Level:Open access
Keyword:Neurociència
Factors neurotròfics
Neurociència cel·lular
Creixement cel·lular
Neuroquímica
Neurotrophic factors
Cellular neuroscience
Cell growth
Neurochemistry
Description
Summary: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.

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