A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration.
Border cell migration in the Drosophila ovary is a relatively simple and genetically tractable model for studying the conversion of epithelial cells to migratory cells. Like many cell migrations, border cell migration is inhibited by a dominant-negative form of the GTPase Rac. To identify new genes that function in Rac-dependent cell motility, we screened for genes that when overexpressed suppressed the migration defect caused by dominant-negative Rac. Overexpression of the Drosophila inhibitor of apoptosis 1 (DIAP1), which is encoded by the thread (th) gene, suppressed the migration defect. Moreover, loss-of-function mutations in th caused migration defects but, surprisingly, did not cause apoptosis. Mutations affecting the Dark protein, an activator of the upstream caspase Dronc, also rescued RacN17 migration defects. These results indicate an apoptosis-independent role for DIAP1-mediated Dronc inhibition in Rac-mediated cell motility.
Geisbrecht
Erika R
ER
Department of Biological Chemistry, Johns Hopkins School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Montell
Denise J
DJ
D000818:Animals; D061945:Caspase Inhibitors; D002465:Cell Movement; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000378:metabolism; D004330:Drosophila / Q000166:cytology*; D029721:Drosophila Proteins / Q000378:metabolism*; D005260:Female; D017344:Genes, Insect; D051034:Inhibitor of Apoptosis Proteins; D008840:Microfilament Proteins / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D010053:Ovary / Q000166:cytology; D051304:Profilins; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D061945:Caspase Inhibitors; D003285:Contractile Proteins; C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D008840:Microfilament Proteins; D051304:Profilins; C495737:chic protein, Drosophila; D020744:rac GTP-Binding Proteins