Chimaerin and Rac regulate cell number, adherens junctions, and ERK MAP kinase signaling in the Drosophila eye.
The chimaerin family of Rac GTPase-activating proteins (GAPs) has been implicated in neural development and tumor progression, although the cellular mechanisms of their effects are poorly understood. To study their physiologic function, we used the Drosophila retina as a model system. Reduced expression of the fly chimaerin ortholog RhoGAP5a in the pupal eye led to an excess of interommatidial pigment cells, aberrant cell contacts, and an increase in activated ERK that localized specifically to the plasma membrane. Reducing RhoGAP5A levels suppressed the effects of disrupted EGF receptor signaling. Perturbation of Rac activity led to similar phenotypes, whereas coexpression of Rac and RhoGAP5A-dsRNAi resulted in the elimination of adherens junctions between interommatidial cells. Our results reveal a role for chimaerin in the regulation of ERK signaling and cell-cell adhesion and have implications for its participation in epithelial development and tumor progression.
Bruinsma
Stephen P
SP
Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Cagan
Ross L
RL
Baranski
Thomas J
TJ
D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D002452:Cell Count; D020740:Chimerin Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology / Q000254:growth & development; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005123:Eye / Q000201:enzymology* / Q000254:growth & development / Q000473:pathology; D005136:Eye Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D020740:Chimerin Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; C520015:RhoGAP5a protein, Drosophila; C075638:aos protein, Drosophila; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D020744:rac GTP-Binding Proteins