TY - JOUR
T1 - Nuclear contour irregularity and abnormal transporter protein distribution in anterior horn cells in amyotrophic lateral sclerosis
AU - Kinoshita, Yoshimi
AU - Ito, Hidefumi
AU - Hirano, Asao
AU - Fujita, Kengo
AU - Wate, Reika
AU - Nakamura, Masataka
AU - Kaneko, Satoshi
AU - Nakano, Satoshi
AU - Kusaka, Hirofumi
PY - 2009/11
Y1 - 2009/11
N2 - The nucleocytoplasmic transport system is essential for maintainingcell 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 thenuclear 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-β 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.
AB - The nucleocytoplasmic transport system is essential for maintainingcell 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 thenuclear 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-β 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.
KW - Amyotrophic lateral sclerosis
KW - Nuclear contour irregularity
KW - Nuclear pore complex
KW - Nucleocytoplasmic transport system
KW - Nucleoporin
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UR - http://www.scopus.com/inward/citedby.url?scp=70449393271&partnerID=8YFLogxK
U2 - 10.1097/NEN.0b013e3181bc3bec
DO - 10.1097/NEN.0b013e3181bc3bec
M3 - Article
C2 - 19816199
AN - SCOPUS:70449393271
SN - 0022-3069
VL - 68
SP - 1184
EP - 1192
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 11
ER -