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p62/sequestosome 1 binds to TDP‐43 in brains with frontotemporal lobar degeneration with TDP‐43 inclusions
Author(s) -
Tanji Kunikazu,
Zhang HaiXin,
Mori Fumiaki,
Kakita Akiyoshi,
Takahashi Hitoshi,
Wakabayashi Koichi
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23081
Subject(s) - frontotemporal lobar degeneration , ubiquitin , sequestosome 1 , cytoplasmic inclusion , immunoprecipitation , biology , cytoplasm , pathogenesis , frontotemporal dementia , pathology , microbiology and biotechnology , antibody , medicine , biochemistry , disease , dementia , genetics , gene , immunoglobulin light chain
Ubiquitin‐positive cytoplasmic inclusions are consistently found in various neurodegenerative diseases. As with ubiquitin, anti‐p62/SQSTM1 (referred to as p62 ) antibody clearly immunostains these inclusions. p62 has a ubiquitin‐associated domain at the carboxyl terminus and thereby interacts with ubiquitinated and misfolded proteins. Here we immunoprecipitated endogenous p62 in the cerebral cortex from patients with frontotemporal lobar degeneration with TDP‐43 inclusions (FTLD‐TDP) and found that p62 coimmunoprecipitated several proteins, including TDP‐43, which is a major disease protein in FTLD‐TDP. Unexpectedly, p62 immunoprecipitated a smaller amount of TDP‐43 in FTLD‐TDP compared with controls. Further analyses showed that p62 physiologically binds to TDP‐43 and likely is involved in degradation of TDP‐43 with 35‐kDa, but not full‐length TDP‐43. Our results suggest that the interaction of TDP‐43 and p62 is disrupted and may participate in the pathogenesis of TDP‐43 proteinopathy. © 2012 Wiley Periodicals, Inc.