Cell-cell adhesion and morphogenesis in Dictyostelium discoideum.
During development of Dictyostelium discoideum, cells acquire EDTA-resistant cell-cell adhesion at the aggregation stage. The EDTA-resistant cell binding activity is associated with a cell surface glycoprotein of Mr 80,000 (gp80), which mediates cell-cell binding via homophilic interaction. Analysis of the structure of gp80 deduced from cDNA sequence reveals the presence of three internally homologous segments in the NH2-terminal domain, which also contains regions with homology to the neural cell adhesion molecule. Secondary structure predictions show an abundance of beta-structures and very few alpha-helices. This is confirmed by circular dichroism measurements. It is likely that the homologous segments are organized into globular structures, extended from the cell surface by a Pro-rich stalk domain. The cell binding activity of gp80 resides within the first globular repeat of the NH2-terminal domain and has been mapped to a 51 amino acid region between Val123 and Leu173. Synthetic oligopeptides corresponding to sequences within this region have been prepared and assayed for their ability to bind to cell surface gp80. Results lead to identification of the homophilic binding site to an octapeptide sequence within this region. Synthetic peptides containing this octapeptide sequence and univalent antibodies directed against this site block the formation of organized cell streams during aggregation. Although cell aggregates are eventually formed, most fail to undergo further development to give rise to slugs and fruiting bodies, indicating that cell-cell adhesion involving gp80 is an important step in normal morphogenesis.
Siu
C H
CH
Banting and Best Department of Medical Research, Charles H. Best Institute, University of Toronto, Ontario, Canada.
Kamboj
R K
RK
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002645:Chickens; D002942:Circular Dichroism; D004023:Dictyostelium / Q000254:growth & development* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D015800:Protozoan Proteins; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C052291:cell cohesion molecule, Dictyostelium