The present address of I.-F. Wang is the Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA.
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TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor
Article first published online: 14 DEC 2007
DOI: 10.1111/j.1471-4159.2007.05190.x
© 2008 The Authors
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How to Cite
Wang, I.-F., Wu, L.-S., Chang, H.-Y. and Shen, C.-K. J. (2008), TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor. Journal of Neurochemistry, 105: 797–806. doi: 10.1111/j.1471-4159.2007.05190.x
Publication History
- Issue published online: 14 DEC 2007
- Article first published online: 14 DEC 2007
- Received September 26, 2007; revised manuscript received November 10, 2007; accepted November 27, 2007.
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Keywords:
- depolarization;
- neuronal dendrites;
- processing body;
- RNA granules;
- RNA-binding proteins;
- TDP-43
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.