Membrane Attack Complex / Perforin-like (MACPF) proteins are best known for their roles in mammalian immunity, where they function to disrupt cell membranes by forming oligomeric pores. However, several MACPF proteins perform essential, but poorly understood, roles in development. The sole Drosophila MACPF protein, Torso-like (Tsl), is well known for its role in early embryonic patterning where our studies suggest it enables secretion of a specific growth factor, Trunk, the ligand for the Torso receptor tyrosine kinase1. We and others have recently discovered that tsl is also expressed in the major fly endocrine gland, the prothoracic gland, where it has an additional role in the regulation of growth and developmental transitions2,3. We have further shown that this role of Tsl is independent of Trunk and Torso3, raising the possibility that Tsl also influences the secretion of other growth factors. tsl null mutants exhibit a delay in time to pupariation and reduced adult body size, phenotypes that closely resemble those observed when insulin signalling is reduced. To investigate a role for Tsl in insulin signalling we performed genetic interaction experiments between tsl and components of the insulin signalling pathway. Over-expression of PI3K in the prothoracic gland results in a shorter time to pupariation. This phenotype is suppressed in a tsl mutant background, providing evidence that Tsl interacts with the insulin signalling pathway. We are currently performing additional genetic interaction experiments to determine where in the pathway Tsl functions, and in addition, whether secretion of insulin-like peptides is impaired in tsl mutants. Finally, we are also screening other candidate growth factors, neuropeptides and their receptors for roles in the prothoracic gland, and testing for interactions with Tsl. Our studies of Tsl will provide fundamental insight into the regulation of important insect growth pathways, many of which play highly conserved roles in humans.
1. Johnson, Henstridge et al. (2015) Nat. Commun. 6, 8759; 2. Grillo et al. (2012) Sci. Rep. 2, 762; 3. Johnson et al. (2013) PNAS 110, 14688-14692.