Plasmamembrane-localization of apoptotic caspases for non-apoptotic functions

Research output: Contribution to journalArticlepeer-review

Authors

  • Alla Amcheslavsky
  • Shiuan Wang
  • Caitlin Fogarty
  • Jillian Lindblad
  • Andreas Bergmann

Colleges, School and Institutes

External organisations

  • Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
  • Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030

Abstract

Caspases are best characterized for their function in apoptosis. However, they also have nonapoptotic functions such as apoptosis-induced proliferation (AiP) where caspases release mitogens for compensatory proliferation independently of their apoptotic role. Here, we report that the unconventional myosin, Myo1D, which is known for its involvement in left/right development, is an important mediator of AiP in Drosophila. Mechanistically, Myo1D translocates the initiator caspase Dronc to the basal side of the plasmamembrane of epithelial cells where Dronc promotes the activation of the NADPH-oxidase Duox for ROS generation and AiP in a non-apoptotic manner. We propose that the basal side of the plasmamembrane constitutes a non-apoptotic compartment for caspases. Finally, Myo1D promotes tumor growth and invasiveness of the neoplastic scrib RasV12 model. Together, we identified a novel function of Myo1D for AiP and tumorigenesis, and reveal a mechanism by which cells sequester apoptotic caspases in a non-apoptotic compartment at the plasmamembrane.

Details

Original languageEnglish
Pages (from-to)450-464.e3
JournalDevelopmental Cell
Volume45
Issue number4
Publication statusPublished - 21 May 2018

Keywords

  • Apoptosis-induced proliferation, Drosophila, Dronc, Myo1D, non-apoptotic functions, plasma membrane