Specific motifs mediate post-synaptic and surface transport of G protein-coupled receptors

Xin Xu, Zhe Wei, Guangyu Wu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

G protein-coupled receptors (GPCRs) are key regulators of synaptic functions. However, their targeted trafficking to synapses after synthesis is poorly understood. Here, we demonstrate that multiple motifs mediate α2B-adrenergic receptor transport to the dendritic and post-synaptic compartments in primary hippocampal neurons, with a single leucine residue on the first intracellular loop being specifically involved in synaptic targeting. The N-terminally located tyrosine-serine motif operates differently in neuronal and non-neuronal cells. We further show that the highly conserved dileucine (LL) motif in the C-terminus is required for the dendritic and post-synaptic traffic of all GPCRs studied. The LL motif also directs the export from the endoplasmic reticulum of a chimeric GPCR and confers its transport ability to vesicular stomatitis virus glycoprotein in cell lines. Collectively, these data reveal the intrinsic structural determinants for the synaptic targeting of nascent GPCRs and their cell-type-specific trafficking along the biosynthetic pathways.

Original languageEnglish (US)
Article number103643
JournaliScience
Volume25
Issue number1
DOIs
StatePublished - Jan 21 2022
Externally publishedYes

Keywords

  • Biological sciences
  • Molecular biology
  • Molecular neuroscience
  • Neuroscience

ASJC Scopus subject areas

  • General

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