Genetic interaction between integrins and moleskin, a gene encoding a Drosophila homolog of importin-7.
The Drosophila PS1 and PS2 integrins are required to maintain the connection between the dorsal and ventral wing epithelia. If alphaPS subunits are inappropriately expressed during early pupariation, the epithelia separate, causing a wing blister. Two lines of evidence indicate that this apparent loss-of-function phenotype is not a dominant negative effect, but is due to inappropriate expression of functional integrins: wing blisters are not generated efficiently by misexpression of loss-of-function alphaPS2 subunits with mutations that inhibit ligand binding, and gain-of-function, hyperactivated mutant alphaPS2 proteins cause blistering at expression levels well below those required by wild-type proteins. A genetic screen for dominant suppressors of wing blisters generated null alleles of a gene named moleskin, which encodes the protein DIM-7. DIM-7, a Drosophila homolog of vertebrate importin-7, has recently been shown to bind the SHP-2 tyrosine phosphatase homolog Corkscrew and to be important in the nuclear translocation of activated D-ERK. Consistent with this latter finding, homozygous mutant clones of moleskin fail to grow in the wing. Genetic tests suggest that the moleskin suppression of wing blisters is not directly related to inhibition of D-ERK nuclear import. These data are discussed with respect to the possible regulation of integrin function by cytoplasmic ERK.
Baker
Scott E
SE
Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA.
Lorenzen
James A
JA
Miller
Steven W
SW
Bunch
Thomas A
TA
Jannuzi
Alison L
AL
Ginsberg
Mark H
MH
Perkins
Lizabeth A
LA
Brower
Danny L
DL
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development; D005786:Gene Expression Regulation; D016153:Genes, Suppressor; D016023:Integrins / Q000235:genetics*; D028884:Karyopherins / Q000235:genetics* / Q000502:physiology; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear
C466996:IPO7 protein, human; D016023:Integrins; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear