A neuropeptide courier for delta-opioid receptors?
The delta-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, report that trafficking of the delta-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 delta-opioid receptor to pain processing is dramatically altered. These observations suggest a new role for peptide precursors as sorting signals in vesicular transport.
Julius
David
D
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California 94143, USA.
Basbaum
Allan I
AI
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D009475:Neurons, Afferent / Q000378:metabolism* / Q000648:ultrastructure; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D011498:Protein Precursors / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D013373:Substance P / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism*
D002352:Carrier Proteins; D011498:Protein Precursors; D017465:Receptors, Opioid, delta; D015320:Tachykinins; C054618:protachykinin; D013373:Substance P