Complex proteolytic processing acts on Delta, a transmembrane ligand for Notch, during Drosophila development.
Delta functions as a cell nonautonomous membrane-bound ligand that binds to Notch, a cell-autonomous receptor, during cell fate specification. Interaction between Delta and Notch leads to signal transduction and elicitation of cellular responses. During our investigations to further understand the biochemical mechanism by which Delta signaling is regulated, we have identified four Delta isoforms in Drosophila embryonic and larval extracts. We have demonstrated that at least one of the smaller isoforms, Delta S, results from proteolysis. Using antibodies to the Delta extracellular and intracellular domains in colocalization experiments, we have found that at least three Delta isoforms exist in vivo, providing the first evidence that multiple forms of Delta exist during development. Finally, we demonstrate that Delta is a transmembrane ligand that can be taken up by Notch-expressing Drosophila cultured cells. Cell culture experiments imply that full-length Delta is taken up by Notch-expressing cells. We present evidence that suggests this uptake occurs by a nonphagocytic mechanism.
Klueg
K M
KM
Department of Biology, Indiana University, Bloomington, Indiana 47405, USA.
Parody
T R
TR
Muskavitch
M A
MA
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000201:enzymology; D029721:Drosophila Proteins; D010450:Endopeptidases / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006868:Hydrolysis; D019476:Insect Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D010587:Phagocytosis; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000378:metabolism; D051880:Receptors, Notch; D013347:Subcellular Fractions / Q000378:metabolism
D029721:Drosophila Proteins; D019476:Insect Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008024:Ligands; D008565:Membrane Proteins; C497759:N protein, Drosophila; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; C064045:delta protein; D010450:Endopeptidases