Neurotrophic actions of a novel molluscan epidermal growth factor

Petra M. Hermann, Ronald E. Van Kesteren, Willem C. Wildering, Sherry D. Painter, John M. Reno, John S. Smith, Santosh B. Kumar, Wijnand P.M. Geraerts, Lowell H. Ericsson, August B. Smit, Andrew G.M. Bulloch, Gregg Thomas Nagle

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The mammalian epidermal growth factor (EGF) is expressed in the developing and adult CNS, and it has been implicated in the control of cell proliferation, differentiation, and neurotrophic events. Despite extensive evolutionary conservation of the EGF motif in a range of different types of proteins, secreted EGF homologs with neurotrophic actions have not been reported in invertebrates. In this study, we present a novel member of the family of EGF-like growth factors, an EGF homolog from the mollusc Lymnaea stagnalis (L-EGF), and we demonstrate that this protein has neurotrophic activity. Purified L-EGF is a 43-residue peptide and retains the typical structural characteristics of the EGF motif. The L-EGF cDNA reveals a unique precursor organization. In contrast to the multidomain mammalian EGFs, it consists of only two domains, a signal peptide and a single EGF motif. Conspicuously, the L-EGF precursor lacks a transmembrane domain, setting it apart from all other members of the EGF-family. L-EGF mRNA is expressed throughout embryonic development, in the juvenile CNS, but not in the normal adult CNS. However, expression in the adult CNS is upregulated after injury, suggesting a role of L-EGF in repair functions. This notion is supported by the observation that L-EGF evokes neurite outgrowth in specific adult Lymnaea neurons in vitro, which could be inhibited by an EGF receptor tyrosine kinase inhibitor. In conclusion, our findings further substantiate the notion that the EGF family has an early phylogenetic origin, and our data support a neurotrophic role for L-EGF during development and injury repair.

Original languageEnglish (US)
Pages (from-to)6355-6364
Number of pages10
JournalJournal of Neuroscience
Volume20
Issue number17
StatePublished - Sep 1 2000

Fingerprint

Epidermal Growth Factor
Lymnaea
Mollusca
Nerve Growth Factors
Wounds and Injuries
Invertebrates
Protein Sorting Signals
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Embryonic Development
Cell Differentiation
Intercellular Signaling Peptides and Proteins

Keywords

  • Development
  • Epidermal growth factor
  • Mollusc
  • Neurite outgrowth
  • Neurotrophic factors
  • Regeneration

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hermann, P. M., Van Kesteren, R. E., Wildering, W. C., Painter, S. D., Reno, J. M., Smith, J. S., ... Nagle, G. T. (2000). Neurotrophic actions of a novel molluscan epidermal growth factor. Journal of Neuroscience, 20(17), 6355-6364.

Neurotrophic actions of a novel molluscan epidermal growth factor. / Hermann, Petra M.; Van Kesteren, Ronald E.; Wildering, Willem C.; Painter, Sherry D.; Reno, John M.; Smith, John S.; Kumar, Santosh B.; Geraerts, Wijnand P.M.; Ericsson, Lowell H.; Smit, August B.; Bulloch, Andrew G.M.; Nagle, Gregg Thomas.

In: Journal of Neuroscience, Vol. 20, No. 17, 01.09.2000, p. 6355-6364.

Research output: Contribution to journalArticle

Hermann, PM, Van Kesteren, RE, Wildering, WC, Painter, SD, Reno, JM, Smith, JS, Kumar, SB, Geraerts, WPM, Ericsson, LH, Smit, AB, Bulloch, AGM & Nagle, GT 2000, 'Neurotrophic actions of a novel molluscan epidermal growth factor', Journal of Neuroscience, vol. 20, no. 17, pp. 6355-6364.
Hermann PM, Van Kesteren RE, Wildering WC, Painter SD, Reno JM, Smith JS et al. Neurotrophic actions of a novel molluscan epidermal growth factor. Journal of Neuroscience. 2000 Sep 1;20(17):6355-6364.
Hermann, Petra M. ; Van Kesteren, Ronald E. ; Wildering, Willem C. ; Painter, Sherry D. ; Reno, John M. ; Smith, John S. ; Kumar, Santosh B. ; Geraerts, Wijnand P.M. ; Ericsson, Lowell H. ; Smit, August B. ; Bulloch, Andrew G.M. ; Nagle, Gregg Thomas. / Neurotrophic actions of a novel molluscan epidermal growth factor. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 17. pp. 6355-6364.
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abstract = "The mammalian epidermal growth factor (EGF) is expressed in the developing and adult CNS, and it has been implicated in the control of cell proliferation, differentiation, and neurotrophic events. Despite extensive evolutionary conservation of the EGF motif in a range of different types of proteins, secreted EGF homologs with neurotrophic actions have not been reported in invertebrates. In this study, we present a novel member of the family of EGF-like growth factors, an EGF homolog from the mollusc Lymnaea stagnalis (L-EGF), and we demonstrate that this protein has neurotrophic activity. Purified L-EGF is a 43-residue peptide and retains the typical structural characteristics of the EGF motif. The L-EGF cDNA reveals a unique precursor organization. In contrast to the multidomain mammalian EGFs, it consists of only two domains, a signal peptide and a single EGF motif. Conspicuously, the L-EGF precursor lacks a transmembrane domain, setting it apart from all other members of the EGF-family. L-EGF mRNA is expressed throughout embryonic development, in the juvenile CNS, but not in the normal adult CNS. However, expression in the adult CNS is upregulated after injury, suggesting a role of L-EGF in repair functions. This notion is supported by the observation that L-EGF evokes neurite outgrowth in specific adult Lymnaea neurons in vitro, which could be inhibited by an EGF receptor tyrosine kinase inhibitor. In conclusion, our findings further substantiate the notion that the EGF family has an early phylogenetic origin, and our data support a neurotrophic role for L-EGF during development and injury repair.",
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AU - Smith, John S.

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AU - Geraerts, Wijnand P.M.

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AU - Bulloch, Andrew G.M.

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