title: FAIM-L regulation of XIAP degradation modulates Synaptic Long-Term Depression and Axon Degeneration.
abstract: Caspases have recently emerged as key regulators of axonal pruning and degeneration and of long-term depression (LTD), a long-lasting form of synaptic plasticity. However, the mechanism underlying these functions remains unclear. In this context, XIAP has been shown to modulate these processes. The neuron-specific form of FAIM protein (FAIM-L) is a death receptor antagonist that stabilizes XIAP protein levels, thus preventing death receptor-induced neuronal apoptosis. Here we show that FAIM-L modulates synaptic transmission, prevents chemical-LTD induction in hippocampal neurons, and thwarts axon degeneration after nerve growth factor (NGF) withdrawal. Additionally, we demonstrate that the participation of FAIM-L in these two processes is dependent on its capacity to stabilize XIAP protein levels. Our data reveal FAIM-L as a regulator of axonal degeneration and synaptic plasticity.
authors: Department of Cell Biology, University of Barcelona, 08028 Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Spain.
authors: Ramón
authors: R
authors: Martínez-Mármol
authors: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Spain.|Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.|Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron (VHIR), 08035 Barcelona, Spain.
authors: Bruna
authors: B
authors: Barneda-Zahonero
authors: Neurophysiology Laboratory, Physiology Unit, Department of Biomedicine, Medical School, Universitat de Barcelona, Barcelona, Spain.|Institute of Neurosciences, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors: David
authors: D
authors: Soto
authors: Department of Cell Biology, University of Barcelona, 08028 Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Spain.
authors: Rosa Maria
authors: RM
authors: Andrés
authors: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Spain.|Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.|Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron (VHIR), 08035 Barcelona, Spain.
authors: Elena
authors: E
authors: Coccia
authors: Neurophysiology Laboratory, Physiology Unit, Department of Biomedicine, Medical School, Universitat de Barcelona, Barcelona, Spain.|Institute of Neurosciences, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors: Xavier
authors: X
authors: Gasull
authors: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Spain.|Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.|Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron (VHIR), 08035 Barcelona, Spain.
authors: Laura
authors: L
authors: Planells-Ferrer
authors: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Spain.|Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.|Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron (VHIR), 08035 Barcelona, Spain.
authors: Rana S
authors: RS
authors: Moubarak
authors: Department of Cell Biology, University of Barcelona, 08028 Barcelona, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Spain.|Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.|Institute of Neurosciences, University of Barcelona, Barcelona, Spain.|ICREA Academia, 08010 Barcelona, Spain.
authors: Eduardo
authors: E
authors: Soriano
authors: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Spain.|Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.|Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron (VHIR), 08035 Barcelona, Spain.
authors: Joan X
authors: JX
authors: Comella
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001369:Axons / Q000378:metabolism; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D051379:Mice; D016202:N-Methylaspartate / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D055550:Protein Stability; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics; D018091:Receptors, AMPA / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; C107521:Birc4 protein, mouse; C498892:Faim protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D018091:Receptors, AMPA; D016202:N-Methylaspartate