title: Nuclear contour irregularity and abnormal transporter protein distribution in anterior horn cells in amyotrophic lateral sclerosis.
abstract: The nucleocytoplasmic transport system is essential for maintaining cell viability; transport of proteins and nucleic acids between the nucleus and the cytoplasm occurs through nuclear pore complexes (NPCs). In this study, we examined the immunohistochemical distribution of the major protein components of NPCs, Nup62, Nup88, and Nup153, in spinal cords from controls and patients with sporadic or familial amyotrophic lateral sclerosis (SALS or FALS) and its mouse model. In control subjects, immunolabeling on the nuclear envelopes of anterior horn cells (AHCs) was invariably smooth and continuous, whereas in SALS and FALS patients, the AHCs predominantly showed irregular nuclear contours. Double immunofluorescence staining demonstrated that in SALS patients, importin-beta immunoreactivity was absent in the nuclei in a subset of AHCs; in these cells, Nup62 immunolabeling of nuclear membrane was invariably irregular, suggesting that there was dysfunctional nucleocytoplasmic transport in those AHCs. In the mouse model, Nup62-immunolabeled AHCs with irregular nuclear contours were predominant as early as the presymptomatic stage and the contours became progressively discontinuous along with disease development. Together, these observations suggest that dysfunctional nucleocytoplasmic transport may underlie the pathogenesis of ALS.
authors.affiliation: Department of Neurology, Kansai Medical University, Moriguchi, Osaka, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Ito
authors.forename: Asao
authors.initials: A
authors.lastname: Hirano
authors.forename: Kengo
authors.initials: K
authors.lastname: Fujita
authors.forename: Reika
authors.initials: R
authors.lastname: Wate
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakano
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kusaka
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000870:Anterior Horn Cells / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D022022:Nuclear Pore / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics
chemical_list: D028861:Nuclear Pore Complex Proteins