The Prohormone Processing Protease amontillado (amon) is Required for Larval Molting in Drosophila. L.Y.M. Rayburn , S. Choksi , M. Bender. Dept Genetics, Univ Georgia, Athens, GA.

   Biosynthesis of most peptide hormones and neuropeptides requires proteolytic excision of the active peptide from inactive proprotein precursors. Endoproteolytic processing of peptide hormones and other secreted and transmembrane proteins is carried out by subtilisin-like proprotein convertases (SPCs) in constitutive and regulated secretory pathways in a variety of cell types. The Drosophila amontillado(amon) gene encodes a homolog of the mammalian PC2 protein, an SPC that functions in the regulated secretory pathway in neuroendocrine tissues. We have identified amon mutants by isolating ethylmethanesulfonate (EMS) induced lethal and visible mutations that define two complementation groups in the amon interval at 97D1 of the third chromosome. DNA sequencing identified the amon complementation group and the DNA sequence change for each of the nine amon alleles isolated. amon mutants arrest during the first to second instar larval molt and can be rescued past this stage by heat-shock induced expression of amon protein. Rescued larvae arrest at the subsequent larval molt, indicating that amon is also required for the second to third instar larval molt. Our data indicate that the amon proprotein convertase is required for larval molting in Drosophila and support a model that amon acts to proteolytically process peptide hormones known to regulate larval ecdysis in insects.