Intranuclear immunolocalization of 14-3-3 protein isoforms in brains with spinocerebellar ataxia type 1.
Immunolocalization of 14-3-3 protein isoforms, one of the interacters with ataxin 1, was investigated in spinocerebellar ataxia type 1 (SCA 1) brains using isoform-specific antibodies. Samples from the pons and from the cerebellum of four SCA1 cases and three controls were studied. The intensity of the immunoreactivity (IR) and its subcellular topography were analyzed. In control subjects, granular immunoreactivity for an epitope common to all known isoforms of 14-3-3 proteins (14-3-3 COM) found in the cytoplasm of some pontine and dentate nucleus neurons was weak. It was observed in some Purkinje cells, while its intensity varied. Many nuclei of those neurons and Purkinje cells of SCA1 were intensely immunopositive for 14-3-3 COM, while it was less in their cytoplasm. Expanded polyglutamine epitope was colocalized to 14-3-3 COM epitope in some pontine neurons, sometimes accumulated in intranuclear inclusion-like structures. This findings support previous reports that 14-3-3 proteins stabilize mutant ataxin 1 in nucleus and possibly lead to neurodegeneration. However, nuclear localization of 14-3-3 proteins in SCA1 brains was dependent on its isoforms, i.e. pontine neurons intensely positive for beta, Purkinje cells for tau and dentate nucleus neurons for both, while all of those neurons were consistently positive for zeta isoform, although sigma isoform tended to be located in the cytoplasm. Nuclear accumulation and isoform- and region-dependent subcellular localizations of 14-3-3 proteins may be related to SCA1 pathology, which exhibits marked regional variability.
Umahara
Takahiko
T
Department of Geriatric Medicine, Tokyo Medical University, and Department of Laboratory Medicine and Pathology, Tokyo Metropolitan Matsuzawa Hospital, Japan. takahiko@tokyo-med.ac.jp
Uchihara
Toshiki
T
Yagishita
Saburo
S
Nakamura
Ayako
A
Tsuchiya
Kuniaki
K
Iwamoto
Toshihiko
T
D048948:14-3-3 Proteins / Q000032:analysis / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D002529:Cerebellar Nuclei / Q000378:metabolism / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D011149:Pons / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D020754:Spinocerebellar Ataxias / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology
D048948:14-3-3 Proteins; D015415:Biomarkers; D010455:Peptides; D020033:Protein Isoforms; C097188:polyglutamine