title: Evidence for secretion of Cu,Zn superoxide dismutase via exosomes from a cell model of amyotrophic lateral sclerosis.
abstract: A familial form of the neurodegenerative disease amyotrophic lateral sclerosis (ALS), is caused by dominant mutations in the cytosolic Cu,Zn superoxide dismutase (SOD1). There has been evidence for secretion of SOD1, by an unknown mechanism. In this work stable mouse motor neuron-like NSC-34 cells overexpressing human SOD1 wild-type hSOD1(wt) (NSC-34/hSOD1(wt)) and mutant hSOD1(G93A) (NSC-34/hSOD1(G93A)) have been used as an ALS cell model. SOD1 was found to be secreted in association with a membrane fraction that pelleted at 100,000xg. Sucrose density gradient separation of this fraction showed that wild-type and mutant SOD1 were found between 0.5 and 1.16M sucrose and co-localized with the exosomal marker CD9. Therefore, SOD1 secretion occurred via exosomes. p115 a cytosolic and Golgi apparatus (GA) protein involved in vesicle tethering was also found in exosomes, contrary to the endoplasmic reticulum protein calnexin. SOD1 secretion mediated by exosomes could explain cell-to-cell transfer of mutant toxicity.
authors.affiliation: Instituto de Tecnologia Química e Biológica, Apartado 127, 2781-901, Oeiras, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Gomes
authors.forename: Sascha
authors.initials: S
authors.lastname: Keller
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
authors.forename: Júlia
authors.initials: J
authors.lastname: Costa
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000473:pathology*; D000818:Animals; D002458:Cell Fractionation / Q000379:methods; D002461:Cell Line, Transformed; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000201:enzymology* / Q000648:ultrastructure*; D009154:Mutation / Q000502:physiology; D022142:Secretory Vesicles / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D013482:Superoxide Dismutase