title: Cytosolic localization of Fox proteins in motor neurons of G93A SOD1 mice.
abstract: NeuN is a nuclear protein expressed exclusively in mature neurons and has served for many years as a reliable neuronal marker in immunohistochemical labeling studies. In 2009, NeuN was identified as Fox3, one of three closely related RNA binding proteins important in pre-mRNA splicing. During the course of a previous study using G93A SOD1 mice, a model of amyotrophic lateral sclerosis (ALS), we observed that NeuN was significantly redistributed to the cytosol. Since altered splicing may be important in the pathogenesis of ALS, we compared the localization (predominantly nuclear or cytosolic) of all three Fox proteins in the lumbar spinal cord of wild-type and G93A SOD1 mice before and after the development of clinical signs of disease. The Fox proteins regulate their own splicing, and we also examined the major Fox protein isoforms in nuclear and cytosolic fractions of lumbar spinal cord by Western blotting. We report here that Fox3 and Fox2 undergo a major cytosolic relocalization in this ALS model that increases with age and that is associated with progressive alterations in the splicing profiles of all three Fox proteins.
authors.affiliation: Department of Medicine, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Ma
authors.affiliation: Faculty of Health, School of Kinesiology and Health Science, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Turnbull
authors.affiliation: Faculty of Health Science, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Eli Prentice
authors.initials: EP
authors.lastname: Crapper
authors.affiliation: Smith School of Business, Queen's University, 99 University Avenue, Kingston, ON, K7L 3N6, Canada.
authors.forename: Henan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medicine, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Drannik
authors.affiliation: Department of Medicine, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada.
authors.forename: Fan
authors.initials: F
authors.lastname: Jiang
authors.affiliation: School of Medicine, Queen's University, 99 University Avenue, Kingston, ON, K7L 3N6, Canada.
authors.forename: Sean
authors.initials: S
authors.lastname: Xia
authors.affiliation: Department of Medicine, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada. turnbull@mcmaster.ca.|Department of Medicine/Neurology, McMaster University, Rm 4U7, Hamilton, ON, L8S 4K1, Canada. turnbull@mcmaster.ca.
authors.forename: John
authors.initials: J
authors.lastname: Turnbull
mesh_terms: D000818:Animals; D003600:Cytosol / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000737:chemistry* / Q000166:cytology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis* / Q000378:metabolism; D000072260:RNA Splicing Factors / Q000032:analysis* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; C558929:Rbfox2 protein, mouse
keywords: ALS; Fox1; Fox2; G93A SOD1; Motor neuron; NeuN/Fox3