Molecular And Physiological Studies Of A Receptor For D-Amino Acid-Containing Neuropeptides In Aplysia

Neuropeptides in several animals undergo an unusual post-translational modification,the isomerization of an amino acid residue from the L-stereoisomer to the D-stereoisomer.The resulting D-amino acid-containing peptide(DAACP)often displays biological activity higher than that of its all-L-residue analogue,with the D-residue being critical for function in many cases.However,little is known about the full physiological roles played by DAACPs,and few studies have examined the interaction of DAACPs with their cognate receptors.Here,we characterized the signaling of several DAACPs derived from a single neuropeptide prohormone,the Aplysia californica achatin-like neuropeptide precursor(apALNP),at their putative receptor,the achatin-like neuropeptide receptor(apALNR).We first used quantitative polymerase chain reaction and in situ hybridization experiments to demonstrate receptor(apALNR)expression throughout the central nervous system;on the basis of the expression pattern,we identified novel physiological functions that may be mediated by apALNR.In addition,the effects of apALNP derived peptides and analogs in receptor assay and in feeding network are similar.These findings support the idea that apALNR is the receptor for apALNP-derived peptides under physiological conditions.Ultimately,these studies provide insight into signaling at one of the few known DAACP specific receptors and advance our understanding of the roles that L-to-D residue isomerization play in neuropeptide signaling.