TY  - GEN
T1  - Protease cleavage at an engineered tetra-basic motif in Drosophila PTTH accelerates developmental timing
AU  - Shimell, MaryJane
AU  - O'Connor, Michael B
DO  - 10.17912/micropub.biology.000168
UR  - http://beta.micropublication.org/journals/biology/micropub-biology-000168/
AB  - In Drosophila melanogaster, the neuropeptide prothoracicotropic hormone (PTTH) is a modulator of metamorphic timing and aids in adaptation to environmental challenges (Shimell et al. 2018). The ptth gene can be found in most insect species, with the exception of Apidae (Skelly et al. 2019), suggesting conservation of structure and function. PTTH binds to its receptor Torso, a receptor tyrosine kinase, to activate a MAPK signaling pathway, which ultimately regulates transcription of the ecdysone biosynthetic genes and the production of ecdysone (McBrayer et al. 2007, Rewitz et al. 2009). Trunk, a paralog of PTTH, also binds Torso, but unlike PTTH, Trunk signals in the early embryo to specify termini cell fates (Duncan et al. 2013). It has been shown that the pro-domain of Trunk is cleaved intracellularly by Furin 1 and Furin 2 at amino acids K75,R76 and that processing is essential for terminal patterning (Henstridge et al. 2014). While prior in vivo and in vitro experiments in Antheraea pernyi (Sauman and Reppert 1996), Manduca sexta (Gilbert et al. 2000), and Helicoverpa armigera (Wei et al. 2005) demonstrated that the recombinant mature fragment of PTTH has the same activity as brain extracts, in each of these cases the negative control was not the pre-propeptide. Only in Bombyx mori has it been shown that mature PTTH, and not the pre-propeptide, is the active species (O’Reilly et al. 1995). Based on these observations, it has been generally accepted that pro-domain processing of PTTH is essential for function. For this reason, we wished to determine if, like Trunk, Drosophila PTTH also requires proteolytic cleavage of the pro-domain to be active.
PY  - 2019
JO  - microPublication Biology
ER  -