SITE-SPECIFIC CLEAVAGE OF BASEMENT-MEMBRANE COLLAGEN-IV DURING DROSOPHILA METAMORPHOSIS

Breakdown of basement membranes is an important step in the controlled rearrangement of cells during metamorphosis, cell migration, and meta static spread of tumor cells. One of our two laboratories found a uniq ue collagenous peptide that only appears during metamorphosis of Droso phila melanogaster. The other laboratory previously reported that duri ng 20-hydroxyecdysone-induced eversion of Drosophila imaginal discs a glycoprotein named gp125 arises (Birr et al., 1990). We show that thes e two peptides are identical and that they are formed from basement me mbrane collagen IV. Cleavage occurs at an imperfection of this homotri meric collagen helix between residues 755/756 in the sequence CALDE/IK MPAK. The peptide is the carboxyl fragment, 100,647 M(r), as derived f rom the amino acid sequence of the collagen alpha1(IV) chain. The corr esponding amino fragment was also recovered from a disulfide-linked ag gregate. This specific cleavage supports the concept of highly targete d, controlled breakdown of basement membranes during metamorphosis. Fu rthermore, these cuts occur at strategic sites of the predicted supram olecular network of collagen IV molecules of Drosophila basement membr anes.