Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein

Nat Cell Biol. 2001 May;3(5):492-8. doi: 10.1038/35074561.


Many structural determinants for G protein-coupled receptor (GPCR) functions have been defined, but little is known concerning the regulation of their transport from the endoplasmic reticulum (ER) to the cell surface. Here we show that a carboxy-terminal hydrophobic motif, FxxxFxxxF, which is highly conserved among GPCRs, functions independently as an ER-export signal for the dopamine D1 receptor. A newly identified ER-membrane-associated protein, DRiP78, binds to this motif. Overexpression or sequestration of DRiP78 leads to retention of D1 receptors in the ER, reduced ligand binding, and a slowdown in the kinetics of receptor glycosylation. Our results indicate that DRiP78 may regulate the transport of a GPCR by binding to a specific ER-export signal.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Biological Transport
  • CD8 Antigens / metabolism
  • Cell Line
  • Cell Membrane / metabolism*
  • Cyclic AMP / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Green Fluorescent Proteins
  • Humans
  • Kinetics
  • Ligands
  • Luminescent Proteins / metabolism
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Models, Biological
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / metabolism
  • Receptors, Dopamine D1 / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Time Factors
  • Two-Hybrid System Techniques


  • CD8 Antigens
  • Ligands
  • Luminescent Proteins
  • Receptors, Cell Surface
  • Receptors, Dopamine D1
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Cyclic AMP

Associated data

  • GENBANK/AF351783
  • GENBANK/AF351784