Identification of mutants in the Drosophila prohormone convertase gene amontillado (amon). L.Y. Rayburn , H. Gooding , S. Choksi , M. Bender. Dept Genetics, Univ Georgia, Athens, GA.

   The subtilisin-like proprotein convertases are responsible for the processing of many important peptide hormones. Because many peptide hormones are synthesized as inactive precursors, it is important that they are activated in a time and tissue specific manner in order to ensure proper function. Seven proprotein convertases have been identified in vertebrates thus far. One, prohormone convertase 2 (PC2), is expressed in neural tissues and is responsible for the processing of proinsulin, proglucagon, and pro-opiomelanocortin. A Drosophila homolog of PC2 (amon) has been cloned and localized to the 97D1 region on the third chromosome (D. Siekhaus and R. Fuller, 1999). To identify amon mutants, we screened for EMS induced lethal and visible mutations and identified new mutations in the amon interval (D. Tolla, A. Kidd, and M. Bender, unpublished). These mutations comprise two complementation groups, one which defines a new gene in the amon interval. We identified the amon complementation group by sequencing members of both complementation groups. The amon complementation group consists of nine mutant alleles and we have now identified the DNA sequence change for each allele. Three amon mutations are predicted to result in a truncated protein due to a nonsense mutation or to mutations in splice acceptor sites while the remaining six are missense mutations. Phenotypic analysis of the amon mutants suggests that amon is required for molting at the end of the first larval instar. Preliminary data from rescue experiments indicates that we are able to rescue amon mutants to the subsequent larval molt. Together, our data suggests that the amon proprotein convertase is required for larval molting in Drosophila, and therefore may act on peptide hormones known to regulate this process in insects.