Identification of cellular recognition sequence of epimorphin and critical role of cell/epimorphin interaction in lung branching morphogenesis.
A mesenchymal protein, epimorphin, is known to bind directly to the cell surface through its central portion and to act as a signaling molecule for epithelial morphogenesis. Utilizing several recombinant polypeptides and synthetic peptides, we identified the cellular recognition sequence of epimorphin in the central portion of this molecule (amino acids 105-123, NGNRTSVDLRIRRTQHSVL; termed NL-peptide sequence). Interestingly, although a model cell type bound to the NL-peptide as strong as to the full-length epimorphin, this peptide itself didn't induce the cellular functional responses so far tested. We found that the NL-peptide behaved as an antagonist for the endogenous epimorphin and severely perturbed lung branching morphogenesis in organ culture. These results not only revealed a part of the functional mechanism of epimorphin but also demonstrated that cell/ epimorphin interaction through the NL-peptide sequence is a critical step for lung epithelial morphogenesis.
Koshida
S
S
Biomedical R & D Department, Sumitomo Electric Industries, Yokohama, Japan.
Hirai
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology*; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology; D011485:Protein Binding; D015398:Signal Transduction
C504582:Epim protein, mouse; D008562:Membrane Glycoproteins; D010446:Peptide Fragments