COMPLEX PROTEOLYTIC PROCESSING ACTS ON DELTA, A TRANSMEMBRANE LIGAND FOR NOTCH, DURING DROSOPHILA DEVELOPMENT

Delta functions as a cell nonautonomous membrane-bound ligand that bin ds to Notch, a cell-autonomous receptor, during cell fate specificatio n. Interaction between Delta and Notch leads to signal transduction an d elicitation of cellular responses. During our investigations to furt her understand the biochemical mechanism by which Delta signaling is r egulated, we have identified four Delta isoforms in Drosophila embryon ic 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 i n vivo, providing the first evidence that multiple forms of Delta exis t during development. Finally, we demonstrate that Delta is a transmem brane ligand that can be taken up by Notch-expressing Drosophila cultu red cells. Cell culture experiments imply that full-length Delta is ta ken up by Notch-expressing cells. We present evidence that suggests th is uptake occurs by a nonphagocytic mechanism.