The RhoGEF Zizimin-related acts in the Drosophila cellular immune response via the Rho GTPases Rac2 and Cdc42.
Zizimin-related (Zir), a Rho guanine nucleotide exchange factor (RhoGEF) homologous to the mammalian Dock-C/Zizimin-related family, was identified in a screen to find new genes involved in the Drosophila melanogaster cellular immune response against eggs from the parasitoid wasp Leptopilina boulardi. RhoGEFs activate Rho-family GTPases, which are known to be central regulators of cell migration, spreading and polarity. When a parasitoid wasp is recognized as foreign, multiple layers of circulating immunosurveillance cells (haemocytes) should attach to the egg. In Zir mutants this process is disrupted and lamellocytes, a haemocyte subtype, fail to properly encapsulate the wasp egg. Furthermore, macrophage-like plasmatocytes exhibit a strong reduction in their ability to phagocytise Escherichia coli and Staphylococcus aureus bacteria. During encapsulation and phagocytosis Zir genetically interacts with two Rho-family GTPases, Rac2 and Cdc42. Finally, Zir is dispensable for the humoral immune response against bacteria. We propose that Zir is necessary to activate the Rho-family GTPases Rac2 and Cdc42 during the Drosophila cellular immune response.
Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen, UK.
Christopher J
CJ
Sampson
Susanna
S
Valanne
Marie-Odile
MO
Fauvarque
Dan
D
Hultmark
Mika
M
Rämet
Michael J
MJ
Williams
D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D010587:Phagocytosis; D010802:Phylogeny; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D000097766:RAC2 GTP-Binding Protein
D029721:Drosophila Proteins; D019204:GTP-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C090145:Cdc42 protein, Drosophila; C575479:Zir protein, Drosophila