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

254 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

Fingerprint

Frontotemporal Lobar Degeneration
RNA-Binding Proteins
Messenger RNA
Neurons
RNA
Neurodegenerative diseases
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Somatotypes
Proteins
Neuronal Plasticity
Transcription
Dendrites
Neurodegenerative Diseases
Plasticity
Actins
Exons
Assays
Brain
Processing

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor. / Wang, I. Fan; Wu, Lien Szn; Chang, Hsiang Yu; Shen, C. K.James.

In: Journal of Neurochemistry, Vol. 105, No. 3, 01.05.2008, p. 797-806.

Research output: Contribution to journalArticle

Wang, I. Fan ; Wu, Lien Szn ; Chang, Hsiang Yu ; Shen, C. K.James. / TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor. In: Journal of Neurochemistry. 2008 ; Vol. 105, No. 3. pp. 797-806.
@article{a47c975ed5a545d58a05b0ed17638ee3,
title = "TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor",
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.",
keywords = "Depolarization, Neuronal dendrites, Processing body, RNA granules, RNA-binding proteins, TDP-43",
author = "Wang, {I. Fan} and Wu, {Lien Szn} and Chang, {Hsiang Yu} and Shen, {C. K.James}",
year = "2008",
month = "5",
day = "1",
doi = "10.1111/j.1471-4159.2007.05190.x",
language = "English",
volume = "105",
pages = "797--806",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor

AU - Wang, I. Fan

AU - Wu, Lien Szn

AU - Chang, Hsiang Yu

AU - Shen, C. K.James

PY - 2008/5/1

Y1 - 2008/5/1

N2 - 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.

AB - 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.

KW - Depolarization

KW - Neuronal dendrites

KW - Processing body

KW - RNA granules

KW - RNA-binding proteins

KW - TDP-43

UR - http://www.scopus.com/inward/record.url?scp=42449163952&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42449163952&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2007.05190.x

DO - 10.1111/j.1471-4159.2007.05190.x

M3 - Article

VL - 105

SP - 797

EP - 806

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 3

ER -