期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1812, 期 12, 页码 1577-1583出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2011.09.005
关键词
TAR DNA binding protein-43; Protein aggregation; Amyotrophic lateral sclerosis; Frontotemporal lobar degeneration
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [22240037, 22110004, 22770162]
- Naito Foundation
- Grants-in-Aid for Scientific Research [22110004, 22240037, 22770162] Funding Source: KAKEN
Aggregation of TAR DNA binding protein-43 (TDP-43) is a hallmark feature of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Under pathogenic conditions, abnormal cleavage of TDP-43 produces the phosphorylated C-terminal fragments (CTFs), which are enriched in neuronal inclusions; however, molecular properties of those TDP-43 fragments remain to be characterized. Here we show distinct degrees of solubility and phosphorylation among fragments truncated at different sites of TDP-43. Truncations were tested mainly within a second RNA recognition motif (RRM2) of TDP-43; when the truncation site was more C-terminal in an RRM2 domain, a TDP-43 CTF basically became less soluble and more phosphorylated in differentiated Neuro2a cells. We also found that cleavage at the third beta-strand in RRM2 leads to the formation of SDS-resistant soluble oligomers. Molecular properties of TDP-43 fragments thus significantly depend upon its cleavage site, which might reflect distinct molecular pathologies among sub-types of TDP-43 proteinopathies. (C) 2011 Elsevier B.V. All rights reserved.
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