title: Nuclear carrier and RNA-binding proteins in frontotemporal lobar degeneration associated with fused in sarcoma (FUS) pathological changes.
abstract: OBJECTIVE
  We aimed to investigate the role of the nuclear carrier and binding proteins, transportin 1 (TRN1) and transportin 2 (TRN2), TATA-binding protein-associated factor 15 (TAF15) and Ewing's sarcoma protein (EWS) in inclusion body formation in cases of frontotemporal lobar degeneration (FTLD) associated with fused in sarcoma protein (FTLD-FUS).
  
  
  METHODS
  Eight cases of FTLD-FUS (five cases of atypical FTLD-U, two of neuronal intermediate filament inclusion body disease and one of basophilic inclusion body disease) were immunostained for FUS, TRN1, TRN2, TAF15 and EWS. Ten cases of FTLD associated with TDP-43 inclusions served as reference cases.
  
  
  RESULTS
  The inclusion bodies in FTLD-FUS contained TRN1 and TAF15 and, to a lesser extent, EWS, but not TRN2. The patterns of immunostaining for TRN1 and TAF15 were very similar to that of FUS. None of these proteins was associated with tau or TDP-43 aggregations in FTLD.
  
  
  CONCLUSIONS
  Data suggest that FUS, TRN1 and TAF15 may participate in a functional pathway in an interdependent way, and imply that the function of TDP-43 may not necessarily be in parallel with, or complementary to, that of FUS, despite each protein sharing many similar structural elements.
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Y S
authors.initials: YS
authors.lastname: Davidson
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Robinson
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mishra
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: A
authors.initials: A
authors.lastname: Baborie
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: E
authors.initials: E
authors.lastname: Jaros
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Perry
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Cairns
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: A
authors.initials: A
authors.lastname: Richardson
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gerhard
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: D
authors.initials: D
authors.lastname: Neary
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Snowden
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Bigio
authors.affiliation: Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, ManchesterCerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, SalfordDepartment of Neuropathology, Walton Centre for Neurology and Neurosurgery, LiverpoolNeuropathology/Cellular Pathology, Royal Victoria InfirmaryInstitute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UKNorthwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, Illinois, Departments ofNeurologyPathology & Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: D M A
authors.initials: DM
authors.lastname: Mann
mesh_terms: D000328:Adult; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000378:metabolism*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D034802:RNA-Binding Protein EWS / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism*; D028961:beta Karyopherins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C000599550:FUS protein, human; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; C102041:TAF15 protein, human; D035381:TATA-Binding Protein Associated Factors; C108121:TNPO1 protein, human; C503621:TNPO2 protein, human; D028961:beta Karyopherins