A Neuropeptide Courier for δ-Opioid Receptors?

The δ-opioid receptor and the precursor protein of a neuropeptide, substance P, are colocalized in the large dense-core vesicles of pain-sensing neurons. In this issue of Cell, Guan et al. (2005) report that trafficking of the δ-opioid receptor to these vesicles depends on its physical interaction with the substance P domain of its precursor polyprotein (protachykinin). Moreover, in mice lacking this precursor, the contribution of the δ-opioid receptor to pain processing is dramatically altered. These observations suggest a new role for peptide precursors as sorting signals in vesicular transport