title: Subcellular Localization of Matrin 3 Containing Mutations Associated with ALS and Distal Myopathy.
abstract: BACKGROUND
  Mutations in Matrin 3 [MATR3], an RNA- and DNA-binding protein normally localized to the nucleus, have been linked to amyotrophic lateral sclerosis (ALS) and distal myopathies. In the present study, we have used transient transfection of cultured cell lines to examine the impact of different disease-causing mutations on the localization of Matrin 3 within cells.
  
  
  RESULTS
  Using CHO and human H4 neuroglioma cell models, we find that ALS/myopathy mutations do not produce profound changes in the localization of the protein. Although we did observe variable levels of Matrin 3 in the cytoplasm either by immunostaining or visualization of fluorescently-tagged protein, the majority of cells expressing either wild-type (WT) or mutant Matrin 3 showed nuclear localization of the protein. When cytoplasmic immunostaining, or fusion protein fluorescence, was seen in the cytoplasm, the stronger intensity of staining or fluorescence was usually evident in the nucleus. In ~80% of cells treated with sodium arsenite (Ars) to induce cytoplasmic stress granules, the nuclear localization of WT and F115C mutant Matrin 3 was not disturbed. Notably, over-expression of mutant Matrin 3 did not induce the formation of obvious large inclusion-like structures in either the cytoplasm or nucleus.
  
  
  CONCLUSIONS
  Our findings indicate that mutations in Matrin 3 that are associated with ALS and myopathy do not dramatically alter the normal localization of the protein or readily induce inclusion formation.
authors.affiliation: Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America; Santa Fe HealthCare Alzheimer's Disease Research Center, University of Florida, Gainesville, Florida, United States of America.
authors.forename: M Carolina
authors.initials: MC
authors.lastname: Gallego-Iradi
authors.affiliation: Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Clare
authors.affiliation: Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America; Santa Fe HealthCare Alzheimer's Disease Research Center, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Hilda H
authors.initials: HH
authors.lastname: Brown
authors.affiliation: Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Janus
authors.affiliation: Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Jada
authors.initials: J
authors.lastname: Lewis
authors.affiliation: Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America; Santa Fe HealthCare Alzheimer's Disease Research Center, University of Florida, Gainesville, Florida, United States of America.
authors.forename: David R
authors.initials: DR
authors.lastname: Borchelt
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D049310:Distal Myopathies / Q000235:genetics / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C518587:MATR3 protein, human; D034521:Nuclear Matrix-Associated Proteins; D016601:RNA-Binding Proteins