THE DROSOPHILA STUBBLE-STUBBLOID GENE ENCODES AN APPARENT TRANSMEMBRANE SERINE-PROTEASE REQUIRED FOR EPITHELIAL MORPHOGENESIS

The Stubble-stubbloid (Sb-sbd) gene is required for hormone-dependent epithelial morphogenesis of imaginal discs of Drosophila, including th e formation of bristles, legs, and wings. The gene has been cloned by using Sb-sbd-associated DNA lesions in a 20-kilobase (kb) region of a 263-kb genomic walk. The region specifies an almost-equal-to 3.8-kb tr anscript that is induced by the steroid hormone 20-hydroxyecdysone in imaginal discs cultured in vitro. The conceptually translated protein is an apparent 786-residue type II transmembrane protein (N terminus i n, C terminus out), including an intracellular N-terminal domain of at least 35 residues and an extracellular C-terminal trypsin-like serine protease domain of 244 residues. Sequence analyses indicate that the Sb-sbd-encoded protease could activate itself by proteolytic cleavage. Consistent with the cell-autonomous nature of the Sb-sbd bristle phen otype, a disulfide bond between cysteine residues in the noncatalytic N-terminal fragment and the C-terminal catalytic fragment could tether the protease to the membrane after activation. Both dominant Sb and r ecessive sbd mutations affect the organization of microfilament bundle s during bristle morphogenesis. We propose that the Sb-sbd product has a dual function. (i) It acts through its proteolytic extracellular do main to detach imaginal disc cells from extra-cellular matrices, and ( ii) it transmits an outside-to-inside signal to its intracellular doma in to modify the cytoskeleton and facilitate cell shape changes underl ying morphogenesis.