Overexpression of HuD, but not of its truncated form HuD I+II, promotes GAP-43 gene expression and neurite outgrowth in PC12 cells in the absence of nerve growth factor

Kimberly D Anderson, Melissa A. Morin, Andrea Beckel-Mitchener, Charlotte D. Mobarak, Rachael L. Neve, Henry M. Furneaux, Richard Burry, Nora I. Perrone-Bizzozero

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

We have previously shown that the RNA-binding protein HuD binds to a regulatory element in the growth-associated protein (GAP)-43 mRNA and that this interaction involves its first two RNA recognition motifs (RRMs). In this study, we investigated the functional significance of this interaction by overexpression of human HuD protein (pcHuD) or its truncated form lacking the third RRM (pcHuD I+II) in PC12 cells. Morphological analysis revealed that pcHuD cells extended short neurites containing GAP-43-positive growth cones in the absence of nerve growth factor (NGF). These processes also contained tubulin and F-actin filaments but were not stained with antibodies against neurofilament M protein. In correlation with this phenotype, pcHuD cells contained higher levels of GAP-43 without changes in levels of other NGF-induced proteins, such as SNAP-25 and tau. In mRNA decay studies, HuD stabilized the GAP-43 mRNA, whereas HuD I+II did not have any effect either on GAP-43 mRNA stability or on the levels of GAP-43 protein. Likewise, pcHuD I+II cells showed no spontaneous neurite outgrowth and deficient outgrowth in response to NGF. Our results indicate that HuD is sufficient to increase GAP-43 gene expression and neurite outgrowth in the absence of NGF and that the third RRM in the protein is critical for this function.

Original languageEnglish
Pages (from-to)1103-1114
Number of pages12
JournalJournal of Neurochemistry
Volume75
Issue number3
DOIs
StatePublished - Sep 11 2000
Externally publishedYes

Fingerprint

GAP-43 Protein
PC12 Cells
Nerve Growth Factor
Gene expression
Gene Expression
Messenger RNA
RNA Stability
RNA
Growth Cones
Proteins
RNA-Binding Proteins
Neurites
Tubulin
Neuronal Outgrowth
Actin Cytoskeleton
Cones
Actins
Phenotype
Antibodies

Keywords

  • Growth-associated protein-43
  • Hu proteins
  • MRNA stability
  • Neurite outgrowth
  • PC12 cells

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Overexpression of HuD, but not of its truncated form HuD I+II, promotes GAP-43 gene expression and neurite outgrowth in PC12 cells in the absence of nerve growth factor. / Anderson, Kimberly D; Morin, Melissa A.; Beckel-Mitchener, Andrea; Mobarak, Charlotte D.; Neve, Rachael L.; Furneaux, Henry M.; Burry, Richard; Perrone-Bizzozero, Nora I.

In: Journal of Neurochemistry, Vol. 75, No. 3, 11.09.2000, p. 1103-1114.

Research output: Contribution to journalArticle

Anderson, Kimberly D ; Morin, Melissa A. ; Beckel-Mitchener, Andrea ; Mobarak, Charlotte D. ; Neve, Rachael L. ; Furneaux, Henry M. ; Burry, Richard ; Perrone-Bizzozero, Nora I. / Overexpression of HuD, but not of its truncated form HuD I+II, promotes GAP-43 gene expression and neurite outgrowth in PC12 cells in the absence of nerve growth factor. In: Journal of Neurochemistry. 2000 ; Vol. 75, No. 3. pp. 1103-1114.
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AU - Morin, Melissa A.

AU - Beckel-Mitchener, Andrea

AU - Mobarak, Charlotte D.

AU - Neve, Rachael L.

AU - Furneaux, Henry M.

AU - Burry, Richard

AU - Perrone-Bizzozero, Nora I.

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