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A Peptide Antagonist of ErbB Receptors, Inherbin3, Induces Neurite Outgrowth from Rat Cerebellar Granule Neurons Through ErbB1 Inhibition

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Abstract

ErbB receptors not only function in cancer, but are also key developmental regulators in the nervous system. We previously identified an ErbB1 peptide antagonist, Inherbin3, that is capable of inhibiting tumor growth in vitro and in vivo. In this study, we found that inhibition of ErbB1 kinase activity and activation of ErbB4 by NRG-1β induced neurite extension, suggesting that ErbB1 and ErbB4 act as negative and positive regulators, respectively, of the neuritogenic response. Inherbin3, inhibited activation not only of ErbB1 but also of ErbB4 in primary neurons, strongly induced neurite outgrowth in rat cerebellar granule neurons, indicating that this effect mainly was due to inhibition of ErbB1 activation.

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Abbreviations

CGNs:

Cerebellar granule neurons

EGFR:

Epidermal growth factor receptor

TGF-α:

Transforming growth factor-α

NRGs:

Neuregulins

TACE:

TNF-α converting enzyme

PI3-K:

Phosphoinositide 3-kinases

CNS:

Central nervous system

NCAM:

Neural cell adhesion molecule

GAP-43:

Growth-associated protein-43

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Acknowledgments

This research was supported in part by Danish Research Councils, Lundbeck Foundation and Danish Cancer Society.

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Authors and Affiliations

  1. Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Symbion, Fruebjergvej 3, 2100, Copenhagen, Denmark

    Ruodan Xu, Stanislava Pankratova, Søren Hofman Christiansen, David Woldbye, Anne Højland, Elisabeth Bock & Vladimir Berezin

  2. ENKAM Pharmaceuticals A/S, Copenhagen, Denmark

    Ruodan Xu

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  1. Ruodan Xu
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  2. Stanislava Pankratova
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  3. Søren Hofman Christiansen
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  4. David Woldbye
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  5. Anne Højland
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  6. Elisabeth Bock
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  7. Vladimir Berezin
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Correspondence to Vladimir Berezin.

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Xu, R., Pankratova, S., Christiansen, S.H. et al. A Peptide Antagonist of ErbB Receptors, Inherbin3, Induces Neurite Outgrowth from Rat Cerebellar Granule Neurons Through ErbB1 Inhibition. Neurochem Res 38, 2550–2558 (2013). https://doi.org/10.1007/s11064-013-1166-1

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  • DOI: https://doi.org/10.1007/s11064-013-1166-1

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