QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 17, 2007, 27(42):11228-11241; doi:10.1523/JNEUROSCI.3462-07.2007

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Segura, M. F. Articles by Comella, J. X. Search for Related Content PubMed PubMed Citation Articles by Segura, M. F. Articles by Comella, J. X.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
The Long Form of Fas Apoptotic Inhibitory Molecule Is Expressed Specifically in Neurons and Protects Them against Death Receptor-Triggered Apoptosis

Miguel F. Segura,¹ Carme Sole,¹ Marta Pascual,³ Rana S. Moubarak,² M. Jose Perez-Garcia,¹ Raffaella Gozzelino,¹ Victoria Iglesias,² Nahuai Badiola,² Jose R. Bayascas,¹ Nuria Llecha,¹ Jose Rodriguez-Alvarez,² Eduardo Soriano,³ Victor J. Yuste,¹ and Joan X. Comella^1,2

¹Cell Signaling and Apoptosis Group, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida-Hospital Universitari Arnau de Vilanova, 25198 Lleida, Spain, ²Institut de Neurociències i Departament Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain, and ³Developmental Neurobiology and Regeneration Unit, Institute for Research in Biomedicine, Parc Cientific de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, and Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain

Correspondence should be addressed to Dr. Joan X. Comella, Institut de Neurociencies i Departament Bioquimica i Biologia Molecular, Universitat Autonoma de Barcelona, 08193 Cerdanyola del Valles, Barcelona, Spain. Email: joan.comella{at}uab.cat

Death receptors (DRs) and their ligands are expressed in developing nervous system. However, neurons are generally resistant to death induction through DRs and rather their activation promotes neuronal outgrowth and branching. These results suppose the existence of DRs antagonists expressed in the nervous system. Fas apoptosis inhibitory molecule (FAIM_S) was first identified as a Fas antagonist in B-cells. Soon after, a longer alternative spliced isoform with unknown function was identified and named FAIM_L. FAIM_S is widely expressed, including the nervous system, and we have shown previously that it promotes neuronal differentiation but it is not an anti-apoptotic molecule in this system. Here, we demonstrate that FAIM_L is expressed specifically in neurons, and its expression is regulated during the development. Expression could be induced by NGF through the extracellular regulated kinase pathway in PC12 (pheochromocytoma cell line) cells. Contrary to FAIM_S, FAIM_L does not increase the neurite outgrowth induced by neurotrophins and does not interfere with nuclear factor B pathway activation as FAIM_S does. Cells overexpressing FAIM_L are resistant to apoptotic cell death induced by DRs such as Fas or tumor necrosis factor R1. Reduction of endogenous expression by small interfering RNA shows that endogenous FAIM_L protects primary neurons from DR-induced cell death. The detailed analysis of this antagonism shows that FAIM_L can bind to Fas receptor and prevent the activation of the initiator caspase-8 induced by Fas. In conclusion, our results indicate that FAIM_L could be responsible for maintaining initiator caspases inactive after receptor engagement protecting neurons from the cytotoxic action of death ligands.

Key words: FAIM; apoptosis; Fas/CD95; TNF; neurotrophic factor; neuron

---

Received Sept. 22, 2006; revised Aug. 28, 2007; accepted Aug. 30, 2007.

Correspondence should be addressed to Dr. Joan X. Comella, Institut de Neurociencies i Departament Bioquimica i Biologia Molecular, Universitat Autonoma de Barcelona, 08193 Cerdanyola del Valles, Barcelona, Spain. Email: joan.comella{at}uab.cat

This article has been cited by other articles:

				H. Kaku and T. L. Rothstein Fas Apoptosis Inhibitory Molecule Enhances CD40 Signaling in B Cells and Augments the Plasma Cell Compartment J. Immunol., August 1, 2009; 183(3): 1667 - 1674. [Abstract] [Full Text] [PDF]

				A. N. Simpkins, R. D. Rudic, D. A. Schreihofer, S. Roy, M. Manhiani, H.-J. Tsai, B. D. Hammock, and J. D. Imig Soluble Epoxide Inhibition Is Protective Against Cerebral Ischemia via Vascular and Neural Protection Am. J. Pathol., June 1, 2009; 174(6): 2086 - 2095. [Abstract] [Full Text] [PDF]

				Y. Murakami, Y. Ikeda, Y. Yonemitsu, M. Onimaru, K. Nakagawa, R.-i. Kohno, M. Miyazaki, T. Hisatomi, M. Nakamura, T. Yabe, et al. Inhibition of Nuclear Translocation of Apoptosis-Inducing Factor Is an Essential Mechanism of the Neuroprotective Activity of Pigment Epithelium-Derived Factor in a Rat Model of Retinal Degeneration Am. J. Pathol., November 1, 2008; 173(5): 1326 - 1338. [Abstract] [Full Text] [PDF]

				L.-y. Yu, M. Saarma, and U. Arumae Death Receptors and Caspases But Not Mitochondria Are Activated in the GDNF- or BDNF-Deprived Dopaminergic Neurons J. Neurosci., July 23, 2008; 28(30): 7467 - 7475. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help