Oral Presentation The 4th Prato Conference on Pore Forming Proteins 2018

The role and function of the Perforin-like protein Torso-like in Drosophila cellular immunity (#12)

Daniel Bakopoulos 1 , Lauren Forbes-Beadle 1 , Katherine M Esposito 1 , Coral G Warr 1 , James C Whisstock 1 , Travis K Johnson 1
  1. Monash University, Clayton, VIC, Australia

Perforin-like proteins are well-known for their roles in vertebrate immunity and bacterial pathogenesis where they form large oligomeric pores on target cells to induce their death. However, several Perforin-like proteins are known to control developmental processes and their mechanisms of action, including whether or not they form pores, remains unclear. To address this, we are studying Torso-like (Tsl) from the fruit fly Drosophila melanogaster. Tsl has long been known to control the activation of a receptor tyrosine kinase (RTK) in the early fly embryo. Precisely how Tsl achieves this is unknown, but several lines of evidence suggest that it regulates the activity or availability of a certain growth factor ligand. Recently, we discovered that Tsl plays an additional key role in the development of the Drosophila cellular immune system. This system is highly tractable when compared to the embryo for both genetic and cell biology approaches. Using these approaches we found that Tsl functions to promote the proliferation of circulating macrophages. Our genetic interaction data implicates Tsl in the activation of a different RTK to the embryo suggesting that Tsl controls multiple cell signalling pathways during fly development; possibly by regulating a common cellular process. These data together with a biochemical characterisation of Tsl function will provide a detailed understanding of how developmental Perforin-like proteins can regulate cellular signalling and whether membrane pore formation is required.