Neurotrophic Actions of a Novel Molluscan Epidermal Growth Factor

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.

Synapse Number and Synaptic Efficacy Are Regulated by Presynaptic cAMP and Protein Kinase A

“…The isolated ganglia were removed, and the CM was frozen at Ϫ20°C until use (up to 6 months). Although the specific composition of various neurotrophic proteins present in the CM is unknown, previous studies have identified at least two Lymnaea trophic molecules that partially mimic the effects of CM on neurite outgrowth [cystine-rich neurotrophic factor (Fainzilber et al, 1996); Lymnaea epidermal growth factor (Hermann et al, 2000)] and synapse formation [Lymnaea epidermal growth factor ].…”

Fundamental Studies oninvivoandinvitroPearl Formation—Contribution of Outer Epithelial Cells of Pearl Oyster Mantle and Pearl Sacs

“…Bioactive peptides, such as transforming growth factor-β, bone morphogenetic protein, basic fibroblast growth factor, and keratinocyte growth factor, are known to mediate mesenchymal-epithelial interactions in the skin, which leads to epithelial regeneration (Yamaguchi et al 2005). In mollusks, the presence of some growth factor peptides has been reported (Hermann et al 2000;Lelong et al 2000;Akalal et al 2003). Further clarification of molluskan growth factors and ECMs and their functional analyses will contribute to the development of tissue culture methods for molluskan cells.…”

The Phylogenetically Conserved Molluscan Chitinase-like Protein 1 (Cg-Clp1), Homologue of Human HC-gp39, Stimulates Proliferation and Regulates Synthesis of Extracellular Matrix Components of Mammalian Chondrocytes

“…Many growth factors are considered to be phylogenetically conserved between Deuterostomes and Protostomes. Examples include the superfamilies of insulin-related peptides (7), epidermal growth factor-related proteins (8), and transforming growth factor-␤-related proteins (6). This opens the possibility of identifying growth factorlike molecules in oysters by homology searching.…”

“…Squiggles represent helices, and arrows represent ␤ strands. Helices and ␤ strands that are part of the (␣␤) 8 barrel are numbered, and secondary elements outside the barrel are labeled with letters. Cg-Clp1 secondary structure elements are predicted using Swissmodel software.…”