Interaction between neuronal intranuclear inclusions and promyelocytic leukemia protein nuclear and coiled bodies in CAG repeat diseases.
Neuronal intranuclear inclusions (NIIs) are a pathological hallmark of CAG repeat diseases. To elucidate the influence of NII formation on intranuclear substructures, we investigated the relationship of NIIs with nuclear bodies in brains of dentatorubral-pallidoluysian atrophy and Machado-Joseph disease. In both diseases, promyelocytic leukemia protein, a major component of the promyelocytic leukemia protein nuclear bodies, altered the normal distribution and was rearranged around NII, forming a single capsular structure. We further demonstrated that NIIs were present in close contact with coiled bodies, a highly dynamic domain that may be involved in the biogenesis of small nuclear ribonucleoproteins. The preferential association of intranuclear polyglutamine aggregates with coiled bodies was also confirmed in the dentatorubral-pallidoluysian atrophy transgenic mouse brain and culture cells expressing mutant atrophin-1. The results suggest that the interaction between NIIs and nuclear bodies may play a role in the pathogenesis of CAG repeat diseases.
Yamada
M
M
Departments of Pathology, Brain Research Institute, Niigata University, Niigata, Japan. nori@bri.niigata-u.ac.jp
Sato
T
T
Shimohata
T
T
Hayashi
S
S
Igarashi
S
S
Tsuji
S
S
Takahashi
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D019556:COS Cells; D002467:Cell Nucleus / Q000502:physiology*; D020541:Coiled Bodies / Q000502:physiology*; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000502:physiology*; D017827:Machado-Joseph Disease / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D020191:Myoclonic Epilepsies, Progressive / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D010455:Peptides / Q000235:genetics; D000071156:Promyelocytic Leukemia Protein; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000502:physiology*; D014162:Transfection; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin / Q000378:metabolism
D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; C095278:atrophin-1; C068921:p80-coilin; C070576:PML protein, human; C097188:polyglutamine