Drosophila awd, the homolog of human nm23, regulates FGF receptor levels and functions synergistically with shi/dynamin during tracheal development.
Human nm23 has been implicated in suppression of metastasis in various cancers, but the underlying mechanism of such activity has not been fully understood. Using Drosophila tracheal system as a genetic model, we examined the function of the Drosophila homolog of nm23, the awd gene, in cell migration. We show that loss of Drosophila awd results in dysregulated tracheal cell motility. This phenotype can be suppressed by reducing the dosage of the chemotactic FGF receptor (FGFR) homolog, breathless (btl), indicating that btl and awd are functionally antagonists. In addition, mutants of shi/dynamin show similar tracheal phenotypes as in awd and exacerbate those in awd mutant, suggesting defects in vesicle-mediated turnover of FGFR in the awd mutant. Consistent with this, Btl-GFP chimera expressed from a cognate btl promoter-driven system accumulate at high levels on tracheal cell membrane of awd mutants as well as in awd RNA duplex-treated cultured cells. Thus, we propose that awd regulates tracheal cell motility by modulating the FGFR levels, through a dynamin-mediated pathway.
Dammai
Vincent
V
Department of Pathology and Laboratory Medicine, and Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Adryan
Boris
B
Lavenburg
Kim R
KR
Hsu
Tien
T
D000818:Animals; D002465:Cell Movement; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology*; D034281:Dynamins / Q000502:physiology*; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D009154:Mutation; D009701:Nucleoside-Diphosphate Kinase / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014132:Trachea / Q000196:embryology*
D029721:Drosophila Proteins; D017468:Receptors, Fibroblast Growth Factor; C102301:BTL protein, Drosophila; D011505:Protein-Tyrosine Kinases; D009701:Nucleoside-Diphosphate Kinase; C061642:awd protein, Drosophila; D034281:Dynamins; C439628:shi protein, Drosophila