Increased expression and localization of the RNA-binding protein HuD and GAP-43 mRNA to cytoplasmic granules in DRG neurons during nerve regeneration

Kimberly D Anderson, M. A. Merhege, M. Morin, F. Bolognani, N. I. Perrone-Bizzozero

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The neuronal-specific RNA-binding protein, HuD, binds to a U-rich regulatory element of the 3′ untranslated region (3′ UTR) of the GAP-43 mRNA and delays the onset of its degradation. We have recently shown that overexpression of HuD in embryonic rat cortical cells accelerated the time course of normal neurite outgrowth and resulted in a twofold increase in GAP-43 mRNA levels. Given this evidence, we sought to investigate the involvement of HuD during nerve regeneration. It is known that HuD protein and GAP-43 mRNA are expressed in the dorsal root ganglia (DRG) of adult rat and that GAP-43 is upregulated in DRG neurons during regeneration. In this study, we examined the expression patterns and levels of HuD and GAP-43 mRNA in DRG neurons following sciatic nerve injury using a combination of in situ hybridization, immunocytochemistry, and quantitative RT-PCR. GAP-43 and HuD expression increased in the ipsilateral DRG during the first 3 weeks of regeneration, with peak values seen at 7 days postcrush. At this time point, the levels of HuD and GAP-43 mRNAs in the ipsilateral DRG increased by twofold and sixfold, respectively, relative to the contralateral DRG. Not only were the temporal patterns of expression of HuD protein and GAP-43 mRNA similar, but also they were found to colocalize in the cytoplasm of DRG neurons. Moreover, both molecules were distributed in cytoplasmic granules containing ribosomal RNA. In conclusion, our results suggest that HuD is involved in the upregulation of GAP-43 expression observed at early stages of peripheral nerve regeneration.

Original languageEnglish
Pages (from-to)100-108
Number of pages9
JournalExperimental Neurology
Volume183
Issue number1
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

Fingerprint

GAP-43 Protein
Cytoplasmic Granules
Nerve Regeneration
RNA-Binding Proteins
Spinal Ganglia
Neurons
Messenger RNA
Regeneration
Ribosomal RNA
3' Untranslated Regions
Sciatic Nerve
Peripheral Nerves
In Situ Hybridization
Cytoplasm
Up-Regulation
Immunohistochemistry
Polymerase Chain Reaction

Keywords

  • ELAV
  • Hu proteins
  • Posttranscriptional regulation
  • RNA-binding protein

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Increased expression and localization of the RNA-binding protein HuD and GAP-43 mRNA to cytoplasmic granules in DRG neurons during nerve regeneration. / Anderson, Kimberly D; Merhege, M. A.; Morin, M.; Bolognani, F.; Perrone-Bizzozero, N. I.

In: Experimental Neurology, Vol. 183, No. 1, 01.09.2003, p. 100-108.

Research output: Contribution to journalArticle

Anderson, Kimberly D ; Merhege, M. A. ; Morin, M. ; Bolognani, F. ; Perrone-Bizzozero, N. I. / Increased expression and localization of the RNA-binding protein HuD and GAP-43 mRNA to cytoplasmic granules in DRG neurons during nerve regeneration. In: Experimental Neurology. 2003 ; Vol. 183, No. 1. pp. 100-108.
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