Characterization of a regulatory unit that controls melanization and affects longevity of mosquitoes |
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Authors: | Chunju?An Aidan?Budd Michael?R?Kanost Email author" target="_blank">Kristin?MichelEmail author |
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Institution: | (1) Division of Biology, Kansas State University, 271 Chalmers Hall, Manhattan, KS 66506, USA;(2) Division of Biology, Kansas State University, 267 Chalmers Hall, Manhattan, KS 66506, USA;(3) European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany;(4) Department of Biochemistry, Kansas State University, 141 Chalmers Hall, Manhattan, KS 66506, USA; |
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Abstract: | Melanization is an innate immune response in arthropods that encapsulates and kills invading pathogens. One of its rate-limiting
steps is the activation of prophenoloxidase (PPO), which is controlled by an extracellular proteinase cascade and serpin inhibitors.
The molecular composition of this system is largely unknown in mosquitoes with the exception of serpin-2 (SRPN2), which was
previously identified as a key negative regulator of melanization. Using reverse genetic and biochemical techniques, we identified
the Anopheles gambiae clip-serine proteinase CLIPB9 as a PPO-activating proteinase, which is inhibited by SRPN2. Double knockdown of SRPN2 and
CLIPB9 reversed the pleiotrophic phenotype induced by SRPN2 silencing. This study identifies the first inhibitory serpin-serine
proteinase pair in mosquitoes and defines a regulatory unit of melanization. Additionally, the interaction of CLIPB9 and SRPN2
affects the life span of adult female mosquitoes and therefore constitutes a well-defined potential molecular target for novel
late-life acting insecticides. |
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