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

Research output: Contribution to journalArticle

261 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)797-806
Number of pages10
JournalJournal of Neurochemistry
Volume105
Issue number3
DOIs
Publication statusPublished - May 1 2008
Externally publishedYes

Keywords

  • Depolarization
  • Neuronal dendrites
  • Processing body
  • RNA granules
  • RNA-binding proteins
  • TDP-43

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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