Diminution of eIF4E activity suppresses parkin mutant phenotypes.
Mutations in the human parkin (PARK2) gene cause autosomal recessive-juvenile Parkinson's disease (AR-JP). In Drosophila melanogaster, mutant parkin alleles display a broad range of phenotypic alterations, including female infertility. Here we report that reducing the level of eukaryotic translation initiation factor 4E (eIF4E) activity specifically rescues the female sterile phenotypes associated with the parkin(P23) mutant allele. Additional defects, including reduction of pupal viability and body size, are also entirely recovered in both male and female flies of the abovementioned genotype. We further show that a null eIF4E-binding protein (4E-BP) allele counteracts the in vivo effects produced, in a parkin(P23) mutant background, by the reduction of functional eIF4E copy number. Moreover, Parkin and eIF4E interact in vitro and co-localize at the posterior end of developing oocytes. Finally, we show that eIF4E is over-expressed in parkin(P23) mutant ovaries as compared to wild-types. Taken together, our data are consistent with the idea that Parkin and eIF4E act in a common pathway, likely modulating cap-dependent translation initiation events.
Ottone
Cristina
C
CEINGE-Biotecnologie Avanzate, Via Comunale Margherita 482, 80145 Naples, Italy.
Galasso
Alessia
A
Gemei
Marica
M
Pisa
Viviana
V
Gigliotti
Silvia
S
Piccioni
Federica
F
Graziani
Franco
F
Verrotti di Pianella
Arturo
A
D000818:Animals; D049628:Body Size / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000254:growth & development / Q000378:metabolism*; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005804:Genes, Lethal; D008297:Male; D009154:Mutation; D010053:Ovary / Q000378:metabolism; D011679:Pupa / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; C105238:cup protein, Drosophila; D044767:Ubiquitin-Protein Ligases; C487430:park protein, Drosophila