The Journal of Neuroscience, September 1, 2000, 20(17):6355-6364
Neurotrophic Actions of a Novel Molluscan Epidermal Growth
Factor
Petra M.
Hermann1,
Ronald E.
van Kesteren2,
Willem C.
Wildering1,
Sherry D.
Painter3,
John M.
Reno5,
John S.
Smith4,
Santosh B.
Kumar5,
Wijnand P. M.
Geraerts2,
Lowell H.
Ericsson5,
August B.
Smit2,
Andrew G. M.
Bulloch1, and
Gregg T.
Nagle3
1 Department of Physiology and Biophysics, Neuroscience
Research Group, University of Calgary, Calgary, Alberta, T2N 4N1
Canada, 2 Department of Molecular and Cellular
Neurobiology, Institute of Neuroscience, Vrije Universiteit, Amsterdam,
1081HV The Netherlands, 3 Marine Biomedical Institute and
Department of Anatomy and Neurosciences and 4 Protein
Chemistry Facility, Department of Human Biological Chemistry and
Genetics, The University of Texas Medical Branch, Galveston, Texas
77555, and 5 Department of Biochemistry, University of
Washington, Seattle, Washington 98195
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.
Key words:
epidermal growth factor; neurotrophic factors; neurite
outgrowth; mollusc; development; regeneration.
Copyright © 2000 Society for Neuroscience 0270-6474/00/20176355-10$05.00/0
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