Web of Science: 10 citations, Scopus: 10 citations, Google Scholar: citations
The death receptor antagonist FLIP-L interacts with Trk and is necessary for neurite outgrowth induced by neurotrophins
Moubarak, Rana S. (Universitat Autònoma de Barcelona. Institut de Neurociències)
Solé, Carme (Institut de Recerca Biomèdica de Lleida)
Pascual, Marta (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Gutiérrez, Humberto (Cardiff University. School of Biosciences)
Llovera, Marta (Institut de Recerca Biomèdica de Lleida)
Pérez García, M. José (Institut de Recerca Biomèdica de Lleida)
Gozzelino, Raffaella (Institut de Recerca Biomèdica de Lleida)
Segura, Miguel F. (Institut de Recerca Biomèdica de Lleida)
Iglesias Guimarais, Victoria (Universitat Autònoma de Barcelona. Institut de Neurociències)
Reix, Stéphanie (Universitat Autònoma de Barcelona. Institut de Neurociències)
Soler, Rosa M. (Institut de Recerca Biomèdica de Lleida)
Davies, Alun M. (Cardiff University. School of Biosciences)
Soriano García, Eduardo (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Yuste Mateos, Víctor J. (Víctor José) (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Comella i Carnicé, Joan Xavier, 1963- (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date: 2010
Abstract: FLICE-inhibitory protein (FLIP) is an endogenous inhibitor of the signaling pathway triggered by the activation of death receptors. Here, we reveal a novel biological function for the long form of FLIP (FLIP-L) in neuronal differentiation, which can be dissociated from its antiapoptotic role. We show that FLIP-L is expressed in different regions of the mouse embryonic nervous system. Immunohistochemistry of mouse brain sections at different stages reveals that, in neurons, FLIP is expressed early during the embryonic neuronal development (embryonic day 16) and decreases at later stages (postnatal days 5–15), when its expression is essentially detected in glial cells. FLIP-L overexpression significantly enhances neurotrophin-induced neurite outgrowth in motoneurons, superior cervical ganglion neurons, and PC12 cells. Conversely, the downregulation of FLIP-L protein levels by specific RNA interference significantly reduces neurite outgrowth, even in the presence of the appropriate neurotrophin stimulus. Moreover, NGF-dependent activation of two main intracellular pathways involved in the regulation of neurite outgrowth, extracellular signal-regulated kinases (ERKs) and nuclear factor ĸB (NF-ĸB), is impaired when endogenous FLIP-L is downregulated, although TrkA remains activated. Finally, we demonstrate that FLIP-L interacts with TrkA, and not with p75NTR, in an NGF-dependent manner, and endogenous FLIP-L interacts with TrkB in wholebrain lysates from embryonic day 15 mice embryos. Altogether, we uncover a new role for FLIP-L as an unexpected critical player in neurotrophin-induced mitogen-activated protein kinase/ERK- and NF-ĸB-mediated control of neurite growth in developing neurons.
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials i que es distribueixin sota la mateixa llicència que regula l'obra original. Cal que es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Apoptosi ; Funcions neurotròfiques ; Neurones ; Creixement
Published in: The Journal of neuroscience, Vol. 30 Núm. 17 (April 2010) , p. 6094-6105, ISSN 1529-2401

DOI: 10.1523/JNEUROSCI.0537-10.2010
PMID: 20427667

12 p, 2.0 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2014-10-14, last modified 2019-08-05

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