Membrane tethered bursicon constructs as heterodimeric modulators of the Drosophila G protein-coupled receptor rickets.

ABSTRACT: The study of complex heterodimeric peptide ligands has been hampered by a paucity of pharmacological tools. To facilitate such investigations, we have explored the utility of membrane tethered ligands (MTLs). Feasibility of this recombinant approach was explored with a focus on Drosophila bursicon, a heterodimeric cystine-knot protein that activates the G protein-coupled receptor rickets (rk). Rk/bursicon signaling is an evolutionarily conserved pathway in insects required for wing expansion, cuticle hardening, and melanization during development. We initially engineered two distinct MTL constructs, each composed of a type II transmembrane domain, a peptide linker, and a C terminal extracellular ligand that corresponded to either the α or β bursicon subunit. Coexpression of the two complem

SUBMITTER: Harwood BN 

PROVIDER: S-EPMC3608437 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature