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James W Fristrom

Publications and source records attributed to James W Fristrom.

3 recordsLinked to original sources

Mutational analysis of Stubble-stubbloid gene structure and function in Drosophila leg and bristle morphogenesis.

The Stubble-stubbloid (Sb-sbd) gene is required for ecdysone-regulated epithelial morphogenesis of imaginal tissues during Drosophila metamorphosis. Mutations in Sb-sbd are associated with defects in apical cell shape changes critical for the evagination of the leg imaginal disc and with defects in assembly and extension of parallel actin bundles in growing mechanosensory bristles. The Sb-sbd gene encodes a type II transmembrane serine protease (TTSP). Here we use a Sb-sbd transgenic construct to rescue both bristle and leg morphogenesis defects in Sb-sbd mutations. Molecular characterization of Sb-sbd mutations and rescue experiments with wild-type and modified Sb-sbd transgenic constructs show that the protease domain is required for both leg and bristle functions. Truncated proteins that express the noncatalytic domains without the protease have dominant effects in bristles but not in legs. Leg morphogenesis, but not bristle growth, is sensitive to Sb-sbd overexpression. Antibody localization of the Sb-sbd protein shows apical expression in elongating legs. Sb-sbd protein is found in the base and shaft in budding bristles and then concentrates at the growing tip when bristles are elongating rapidly. We propose a model whereby Sb-sbd helps coordinate proteolytic modification of extracellular matrix attachments with cytoskeletal changes in both legs and bristles.

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Genetic interactions between the RhoA and Stubble-stubbloid loci suggest a role for a type II transmembrane serine protease in intracellular signaling during Drosophila imaginal disc morphogenesis.

The Drosophila RhoA (Rho1) GTPase is essential for postembryonic morphogenesis of leg and wing imaginal discs. Mutations in RhoA enhance leg and wing defects associated with mutations in zipper, the gene encoding the heavy chain of nonmuscle myosin II. We demonstrate here that mutations affecting the RhoA signaling pathway also interact genetically with mutations in the Stubble-stubbloid (Sb-sbd) locus that encodes an unusual type II transmembrane serine protease required for normal leg and wing morphogenesis. In addition, a leg malformation phenotype associated with overexpression of Sb-sbd in prepupal leg discs is suppressed when RhoA gene dose is reduced, suggesting that RhoA and Sb-sbd act in a common pathway during leg morphogenesis. We also characterized six mutations identified as enhancers of zipper mutant leg defects. Three of these genes encode known members of the RhoA signaling pathway (RhoA, DRhoGEF2, and zipper). The remaining three enhancer of zipper mutations interact genetically with both RhoA and Sb-sbd mutations, suggesting that they encode additional components of the RhoA signaling pathway in imaginal discs. Our results provide evidence that the type II transmembrane serine proteases, a class of proteins linked to human developmental abnormalities and pathology, may be associated with intracellular signaling required for normal development.

Animals↗

Talin is essential for integrin function in Drosophila.

We show that the Drosophila gene rhea, isolated because its wing blister phenotype is typical of mutants affecting integrin function, encodes talin. Embryos deficient in talin have very similar phenotypes to integrin (betaPS) null embryos, including failure in germ band retraction and muscle detachment. We demonstrate that talin is not required for the presence of integrins on the cell surface or their localization at muscle termini. However, talin is required for formation of focal adhesion-like clusters of integrins on the basal surface of imaginal disc epithelia and junctional plaques between muscle and tendon cells. These results indicate that talin is essential for integrin function and acts by stably linking clusters of ECM-linked integrins to the cytoskeleton.

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