Oral Annual Conference of the Genetics Society of Australasia with the NZ Society for Biochemistry & Molecular Biology

Torso-like interacts with the insulin signalling pathway to regulate growth and developmental timing (748)

M A Henstridge 1 , L Aulsebrooke 1 , C K Mirth 1 , Coral Warr 1
  1. School of Biological Sciences, Monash University, Clayton, VIC 3800, Australia

Membrane Attack Complex / Perforin-like (MACPF) proteins are best known for roles in mammalian immunity, where they function to disrupt cell membranes by forming oligomeric pores. However, several MACPF proteins instead perform roles in development. The Drosophila MACPF protein, Torso-like (Tsl), is well known for its role in activating the Torso (Tor) receptor tyrosine kinase to pattern the embryo termini, and our studies suggest it does so by enabling extracellular accumulation of the Tor ligand Trunk1. Tor and Tsl also play roles later in development in growth and developmental timing. Tor functions in the prothoracic gland (PG) as the receptor for prothoracicotropic hormone (PTTH), and tor mutants show developmental delay and increased body size2,3. While Tsl is also expressed in the PG, and tsl mutants show developmental delay, tor:tsl double mutants show a much more severe delay than either single mutation alone4. This suggests that Tsl can act independently of Tor in growth. In support of this, tsl mutants have a smaller body size, not larger as seen with loss of function of PTTH/Tor signalling. In fact the phenotype of tsl mutants more closely resembles that of mutations in the insulin signalling pathway. To investigate this we performed metabolic studies and found that tsl mutants have increased hemolymph glucose and triglyceride content but unchanged hemolymph trehalose levels, consistent with the known metabolic phenotype of insulin pathway mutants. In addition, tsl mutants display reduced nutritional plasticity in a similar manner to chico mutants. We have also performed genetic interaction experiments between tsl and components of the insulin signalling pathway. Over-expression of PI3K in the prothoracic gland using phm-Gal4 results in a shorter time to pupariation, and this phenotype is fully suppressed in a tsl mutant background. Conversely, the reduced pupariation time caused by InRCA overexpression is not suppressed by loss of Tsl, suggesting that Tsl acts upstream of InR. We therefore tested for interaction with the dILPs. Flies lacking three dILPs (2, 3 and 5) show a greatly extended time to pupariation, and this is not rescued by removal of Tsl. Taken together, our data suggests that Tsl plays a role in activation of the insulin receptor by the dILPs.


  1. Johnson, Henstridge et al. (2015) Nat. Commun. 6, 8759; 2. Rewitz et al. (2009) Science 5958, 1403-1405 ; 3. Grillo et al. (2012) Sci. Rep. 2, 762; 4. Johnson et al. (2013) PNAS 110, 14688-14692