Apoptosis

, Volume 16, Issue 3, pp 235–248

The role of IAP antagonist proteins in the core apoptosis pathway of the mosquito disease vector Aedes aegypti

Original Paper

Abstract

While apoptosis regulation has been studied extensively in Drosophila melanogaster, similar studies in other insects, including disease vectors, lag far behind. In D. melanogaster, the inhibitor of apoptosis (IAP) protein DIAP1 is the major negative regulator of caspases, while IAP antagonists induce apoptosis, in part, by binding to DIAP1 and inhibiting its ability to regulate caspases. In this study, we characterized the roles of two IAP antagonists, Michelob_x (Mx) and IMP, in apoptosis in the yellow fever mosquito Aedes aegypti. Overexpression of Mx or IMP caused apoptosis in A. aegypti Aag2 cells, while silencing expression of mx or imp attenuated apoptosis. Addition of recombinant Mx or IMP, but not cytochrome c, to Aag2 cytosolic extract caused caspase activation. Consistent with this finding, AeIAP1 bound and inhibited both initiator and effector caspases from A. aegypti, and Mx and IMP competed with caspases for binding to AeIAP1. However, a difference was observed in the BIR domains responsible for Dronc binding by AeIAP1 versus DIAP1. These findings demonstrate that the mechanisms by which IAP antagonists regulate apoptosis are largely conserved between A. aegypti and D. melanogaster, although subtle differences exist.

Keywords

Apoptosis IAP antagonist IAP Caspase Mosquito Dronc 

Supplementary material

10495_2011_575_MOESM1_ESM.pdf (449 kb)
Supplementary material 1 (PDF 449 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Molecular, Cellular, and Developmental Biology Program, Arthropod Genomics Center, Division of BiologyKansas State UniversityManhattanUSA
  2. 2.Department of Molecular BiologyUniversity of Texas Southwestern Medical CenterDallasUSA

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