Understanding Drosophila Moleskin Function in Cell Adhesion and Signaling

Stephanie Si Tang
University of Arizona

Moleskin (msk), a gene encoding the Drosophila homolog of vertebrate importin-7, has been shown to interact genetically with integrins in cell adhesion and signaling pathways in situ. Integrins are receptor proteins on the cell surface that connect cells to the extra-cellular matrix (ECM). moleskin was identified in a genetic screen for suppression of the dominant wing blistering phenotype caused by inappropriate function of Drosophila PS2 integrins, and was found to be involved in the nuclear translocation of activated D-ERK, a MAP kinase. The exact mechanism of action of moleskin and its interactions with integrins however is still unclear. Using a genetic screen in which wild-type flies were mutagenesized using EMS, we hoped to generate multiple random missense mutations in different regions of the moleskin protein. All present mutants alleles for the two genes completely eliminate protein function, thus we hope to identify new alleles that show hypomorphic or dominant negative phenotypes that might help us better understand the functioning of the protein itself and its interactions in the integrin pathways. Seventeen mutants were isolated from a screen of 13,044 EMS-mutagenized flies. Genetic tests revealed that two of the mutants, due to their failure to complement each other and their ability to complement all msk mutants except for one, were a distinct class of mutants from the screen. Animals that are heterozygous for both moleskin and these new mutants produce blistering in the wing and thickening of the wing veins. This shows the possible involvement of a previously unidentified gene in the integrin pathway. My future work will be aimed at the molecular identification of this new gene.