Nerve growth factor-regulated emergence of functional δ-opioid receptors

Bihua Bie, Zhi Zhang, You Qing Cai, Wei Zhu, Yong Zhang, Jaile Dai, Charles J. Lowenstein, Edward J. Weinman, Zhizhong Z. Pan

Research output: Contribution to journalArticle

Abstract

Sorting of intracellular G-protein-coupled receptors (GPCRs) either to lysosomes for degradation or to plasma membrane for surface insertion and functional expression is a key process regulating signaling strength of GPCRs across the plasma membrane in adult mammalian cells. However, little is known about the molecular mechanisms governing the dynamic process of receptor sorting to the plasma membrane for functional expression under normal and pathological conditions. In this study, we demonstrate that δ-opioid receptor (DOPr), a GPCR constitutively targeted to intracellular compartments, is driven to the surface membrane of central synaptic terminals and becomes functional by the neurotrophin nerve growth factor (NGF) in native brainstem neurons. The NGF-triggered DOPr translocation is predominantly mediated by the signaling pathway involving the tyrosine receptor kinase A, Ca2+-mobilizing phospholipase C, and Ca2+/calmodulin-dependent protein kinase II. Importantly, it requires interactions with the cytoplasmic sorting protein NHERF-1 (Na+/H+ exchange regulatory factor-1) and N-ethyl-maleimide-sensitive factor-regulated exocytosis. In addition, this NGF-mediated mechanism is likely responsible for the emergence of functional DOPr induced by chronic opioids. Thus, NGF may function as a key molecular switch that redirects the sorting of intracellularly targeted DOPr to plasma membrane, resulting in new functional DOPr on central synapses under chronic opioid conditions. Copyright

Original languageEnglish (US)
Pages (from-to)5617-5628
Number of pages12
JournalJournal of Neuroscience
Volume30
Issue number16
DOIs
StatePublished - Apr 21 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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    Bie, B., Zhang, Z., Cai, Y. Q., Zhu, W., Zhang, Y., Dai, J., Lowenstein, C. J., Weinman, E. J., & Pan, Z. Z. (2010). Nerve growth factor-regulated emergence of functional δ-opioid receptors. Journal of Neuroscience, 30(16), 5617-5628. https://doi.org/10.1523/JNEUROSCI.5296-09.2010