title: Death of motoneurons induced by trophic deprivation or by excitotoxicity is not prevented by overexpression of SMN.
abstract: The telomeric copy of the survival motor neuron gene (SMN1) is deleted or mutated in all spinal muscular atrophy (SMA) patients and these patients present mainly a loss in spinal motoneurons. Although studies performed in HeLa cells suggest that SMN may be involved in the biogenesis and possibly in recycling of spliceosomal small nuclear ribonucleoproteins (snRNPs), no link has been established between this function and the consequence of the absence of SMN in the specific loss of motoneurons. We attempted to answer the question of whether SMN plays a direct role in motoneuron survival by transducing cultured motoneurons with lentiviral vectors coding either for an antisense Smn mRNA or for full-length or truncated forms of SMN. We studied their effect on survival under different anti- or proapoptotic culture conditions. Our results show that increased levels of SMN are unable to protect motoneurons from death induced by trophic deprivation or by excitotoxicity. These results suggest that SMN is not a survival factor per se for motoneurons. In addition, overexpression of a truncated form of SMN shown to induce a modified subcellular localization and to exert a dominant-negative effect on snRNP biogenesis and RNA splicing in HeLa cells was ineffective in modifying both localization and survival in motoneurons.
authors: INSERM U.382, CNRS-INSERM-Univ. Mediterranee-AP, Marseille, France.
authors: C
authors: C
authors: Cisterni
authors: S
authors: S
authors: Kallenbach
authors: F
authors: F
authors: Jordier
authors: C
authors: C
authors: Bagnis
authors: B
authors: B
authors: Pettmann
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000235:genetics*; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein; D005333:Fetus; D005822:Genetic Vectors; D006801:Humans; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D016086:Lentivirus / Q000235:genetics; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D009414:Nerve Growth Factors / Q000172:deficiency* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism* / Q000494:pharmacology; D016372:RNA, Antisense / Q000235:genetics; D016601:RNA-Binding Proteins; D051381:Rats; D055532:SMN Complex Proteins; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D055533:Survival of Motor Neuron 1 Protein; D014161:Transduction, Genetic
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D016372:RNA, Antisense; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein; C012301:domoic acid; D007608:Kainic Acid