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TDP‐43, the signature protein of FTLD‐U, is a neuronal activity‐responsive factor
Author(s) -
Wang I.Fan,
Wu LienSzn,
Chang HsiangYu,
Shen C.K. James
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.05190.x
Subject(s) - frontotemporal lobar degeneration , colocalization , messenger rna , biology , stress granule , translation (biology) , microbiology and biotechnology , rna binding protein , rna , transcription factor , neuroscience , frontotemporal dementia , gene , genetics , pathology , medicine , dementia , disease
TDP‐43, recently identified as a signature protein of the pathogenic inclusions in the brains cells of frontotemporal lobar degeneration patients, is a 43 kDa RNA‐binding protein. It has been known mainly as a nuclear factor capable of repressing transcription and promoting exon exclusion. TDP‐43 also forms distinct nuclear substructures linking different types of nuclear bodies. In this study, we provide the first evidence supporting TDP‐43 as a neuronal activity‐responsive factor in the dendrites of hippocampal neurons. In particular, TDP‐43 resides in the somatodendrites mainly in the form of RNA granules colocalized with the post‐synaptic protein PSD‐95. These granules also contain RNAs including at least the β‐actin mRNA and CaMKIIα mRNA. Furthermore, TDP‐43 is localized in the dendritic processing (P) body and it behaves as a translational repressor in an in vitro assay. Related to this, repetitive stimuli by KCl greatly enhance the colocalization of TDP‐43 granules with FMRP and Staufen 1, two RNA‐binding proteins known to regulate mRNA transport and local translation in neurons. These data together suggest that TDP‐43 is a neuronal activity‐responsive factor functioning in the regulation of neuronal plasticity, the impairment of which would lead to the development of certain forms of neurodegenerative diseases including frontotemporal lobar degeneration.