Dataset Information

A90V TDP-43 variant results in the aberrant localization of TDP-43 in vitro.

ABSTRACT: TAR DNA-binding protein-43 (TDP-43) is a highly conserved, ubiquitously expressed nuclear protein that was recently identified as the disease protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). Pathogenic TDP-43 gene (TARDBP) mutations have been identified in familial ALS kindreds, and here we report a TARDBP variant (A90V) in a FTLD/ALS patient with a family history of dementia. Significantly, A90V is located between the bipartite nuclear localization signal sequence of TDP-43 and the in vitro expression of TDP-43-A90V led to its sequestration with endogenous TDP-43 as insoluble cytoplasmic aggregates. Thus, A90V may be a genetic risk factor for FTLD/ALS because it predisposes nuclear TDP-43 to redistribute to the cytoplasm and form pathological aggregates.

SUBMITTER: Winton MJ

PROVIDER: S-EPMC2478749 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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A90V TDP-43 variant results in the aberrant localization of TDP-43 in vitro.

Winton Matthew J MJ Van Deerlin Vivianna M VM Kwong Linda K LK Yuan Wuxing W Wood Elisabeth McCarty EM Yu Chang-En CE Schellenberg Gerard D GD Rademakers Rosa R Caselli Richard R Karydas Anna A Trojanowski John Q JQ Miller Bruce L BL Lee Virginia M-Y VM

FEBS letters 20080527 15

TAR DNA-binding protein-43 (TDP-43) is a highly conserved, ubiquitously expressed nuclear protein that was recently identified as the disease protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). Pathogenic TDP-43 gene (TARDBP) mutations have been identified in familial ALS kindreds, and here we report a TARDBP variant (A90V) in a FTLD/ALS patient with a family history of dementia. Significantly, A90V is located between ...[more]

PMID: 18505686

Dataset Information

A90V TDP-43 variant results in the aberrant localization of TDP-43 in vitro.

Publications

A90V TDP-43 variant results in the aberrant localization of TDP-43 in vitro.

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