TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor

I. Fan Wang, Lien Szn Wu, Hsiang Yu Chang, C. K.James Shen

研究成果: 雜誌貢獻文章同行評審

299 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)797-806
頁數10
期刊Journal of Neurochemistry
105
發行號3
DOIs
出版狀態已發佈 - 5月 1 2008
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 細胞與分子神經科學

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