Collapsin Response Mediator Protein 4a (CRMP4a) Is Upregulated in Motoneurons of Mutant SOD1 Mice and Can Trigger Motoneuron Axonal Degeneration and Cell Death
| Autor: | Laure Duplan, Véronique Rogemond, Jérôme Honnorat, Brigitte Pettmann, Béatrice de Bovis, Philippe Marin, Nathalie Bernard, Christopher E. Henderson, Cédric Raoul, Patrick Aebischer, Eric Thouvenot, Wilfrid Casseron, Keith Dudley |
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| Rok vydání: | 2010 |
| Předmět: |
Proteomics
Programmed cell death Vesicular Acetylcholine Transport Proteins Green Fluorescent Proteins Nerve Tissue Proteins Biology Nitric Oxide Mice Downregulation and upregulation Animals Humans Gene silencing Receptor Cells Cultured Motor Neurons Denervation Cell Death Superoxide Dismutase musculoskeletal neural and ocular physiology General Neuroscience Amyotrophic Lateral Sclerosis fungi Articles Embryo Mammalian musculoskeletal system Fas receptor Axons Mice Mutant Strains Up-Regulation Cell biology Disease Models Animal Electroporation Spinal Cord nervous system Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Nerve Degeneration Collapsin response mediator protein family Signal transduction tissues Neuroscience |
| Zdroj: | The Journal of Neuroscience. 30:785-796 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.5411-09.2010 |
| Popis: | Embryonic motoneurons from mutant SOD1 (mSOD1) mouse models of amyotrophic lateral sclerosis (ALS), but not wild-type motoneurons, can be triggered to die by exposure to nitric oxide (NO), leading to activation of a motoneuron-specific signaling pathway downstream of the death receptor Fas/CD95. To identify effectors of mSOD1-dependent cell death, we performed a proteomic analysis. Treatment of cultured mSOD1 motoneurons with NO led to a 2.5-fold increase in levels of collapsin response mediator protein 4a (CRMP4a). In vivo, the percentage of mSOD1 lumbar motoneurons expressing CRMP4 in mSOD1 mice increased progressively from presymptomatic to early-onset stages, reaching a maximum of 25%. Forced adeno-associated virus (AAV)-mediated expression of CRMP4a in wild-type motoneuronsin vitrotriggered a process of axonal degeneration and cell death affecting 60% of motoneurons, whereas silencing of CRMP4a in mSOD1 motoneurons protected them from NO-induced death.In vivo, AAV-mediated overexpression of CRMP4a but not CRMP2 led to the death of 30% of the lumbar motoneurons and an 18% increase in denervation of neuromuscular junctions in the gastrocnemius muscle. Our data identify CRMP4a as a potential early effector in the neurodegenerative process in ALS. |
| Databáze: | OpenAIRE |
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