An immune-responsive Serpin regulates the melanization cascade in Drosophila.
In arthropods, the melanization reaction is associated with multiple host defense mechanisms leading to the sequestration and killing of invading microorganisms. Arthropod melanization is controlled by a cascade of serine proteases that ultimately activates the enzyme prophenoloxidase (PPO), which, in turn, catalyzes the synthesis of melanin. Here we report the biochemical and genetic characterization of a Drosophila serine protease inhibitor protein, Serpin-27A, which regulates the melanization cascade through the specific inhibition of the terminal protease prophenoloxidase-activating enzyme. Our data demonstrate that Serpin-27A is required to restrict the phenoloxidase activity to the site of injury or infection, preventing the insect from excessive melanization.
De Gregorio
Ennio
E
Centre de Génétique Moléculaire du CNRS, 91198 Gif-sur-Yvette, France.
Han
Sung-Jun
SJ
Lee
Won-Jae
WJ
Baek
Min-Ji
MJ
Osaki
Tsukasa
T
Kawabata
Shun-Ichiro
S
Lee
Bok-Leul
BL
Iwanaga
Sadaaki
S
Lemaitre
Bruno
B
Brey
Paul T
PT
D000595:Amino Acid Sequence; D000818:Animals; D004156:Catechol Oxidase / Q000276:immunology / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology*; D004792:Enzyme Precursors / Q000276:immunology / Q000378:metabolism; D008543:Melanins / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D015843:Serpins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D029721:Drosophila Proteins; D004792:Enzyme Precursors; D008543:Melanins; D015843:Serpins; C468118:Spn27A protein, Drosophila; C038451:pro-phenoloxidase; D004156:Catechol Oxidase