title: The presence of heterogeneous nuclear ribonucleoproteins in frontotemporal lobar degeneration with FUS-positive inclusions.
abstract: Frontotemporal lobar degeneration with fused in sarcoma-positive inclusions (FTLD-FUS) is a disease with unknown cause. Transportin 1 is abundantly found in FUS-positive inclusions and responsible for the nuclear import of the FET proteins of which FUS is a member. The presence of all FET proteins in pathological inclusions suggests a disturbance of transportin 1-mediated nuclear import. FUS also belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) protein family. We investigated whether hnRNP proteins are associated with FUS pathology implicating dysfunctional nuclear export in the pathogenesis of FTLD-FUS. hnRNP proteins were investigated in affected brain regions in FTLD-FUS using immunohistochemistry, biochemical analysis, and the expression analysis. We demonstrated the presence of several hnRNP proteins in pathological inclusions including neuronal cytoplasmic inclusions and dystrophic neurites. The biochemical analysis revealed a shift in the location of hnRNP A1 from the nucleus to the cytoplasm. The expression analysis revealed an increase in several hnRNP proteins in FTLD-FUS. These results implicate a wider dysregulation of movement between intracellular compartments, than mechanisms only affecting the nuclear import of FUS proteins.
authors: The Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, Institute of Neurology, UCL, London, UK.
authors: Priya
authors: P
authors: Gami-Patel
authors: The Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, Institute of Neurology, UCL, London, UK.
authors: Rina
authors: R
authors: Bandopadhyay
authors: The Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, Institute of Neurology, UCL, London, UK.
authors: Jack
authors: J
authors: Brelstaff
authors: The Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, Institute of Neurology, UCL, London, UK.
authors: Tamas
authors: T
authors: Revesz
authors: The Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, Institute of Neurology, UCL, London, UK. Electronic address: T.Lashley@ucl.ac.uk.
authors: Tammaryn
authors: T
authors: Lashley
mesh_terms: D021581:Active Transport, Cell Nucleus; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000378:metabolism*; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016501:Neurites / Q000378:metabolism; D021381:Protein Transport; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D028961:beta Karyopherins / Q000378:metabolism / Q000502:physiology
chemical_list: C000599550:FUS protein, human; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D034702:RNA-Binding Protein FUS; C108121:TNPO1 protein, human; D028961:beta Karyopherins
keywords: FET proteins; FUS; Frontotemporal dementia; NanoString; Transportin; hnRNP