ANKRD13C acts as a molecular chaperone for G protein-coupled receptors

J Biol Chem. 2010 Dec 24;285(52):40838-51. doi: 10.1074/jbc.M110.142257. Epub 2010 Oct 19.


Although the mechanisms that regulate folding and maturation of newly synthesized G protein-coupled receptors are crucial for their function, they remain poorly characterized. By yeast two-hybrid screening, we have isolated ANKRD13C, a protein of unknown function, as an interacting partner for the DP receptor for prostaglandin D(2). In the present study we report the characterization of this novel protein as a regulator of DP biogenesis and trafficking in the biosynthetic pathway. Co-localization by confocal microscopy with an endoplasmic reticulum (ER) marker, subcellular fractionation experiments, and demonstration of the interaction between ANKRD13C and the cytoplasmic C terminus of DP suggest that ANKRD13C is a protein associated with the cytosolic side of ER membranes. Co-expression of ANKRD13C with DP initially increased receptor protein levels, whereas siRNA-mediated knockdown of endogenous ANKRD13C decreased them. Pulse-chase experiments indicated that ANKRD13C can promote the biogenesis of DP by inhibiting the degradation of newly synthesized receptors. However, a prolonged interaction between ANKRD13C and DP resulted in ER retention of misfolded/unassembled forms of the receptor and to their proteasome-mediated degradation. ANKRD13C also regulated the expression of other GPCRs tested (CRTH2, thromboxane A(2) (TPα), and β2-adrenergic receptor), whereas it did not affect the expression of green fluorescent protein, GRK2 (G protein-coupled receptor kinase 2), and VSVG (vesicular stomatitis virus glycoprotein), showing specificity toward G protein-coupled receptors. Altogether, these results suggest that ANKRD13C acts as a molecular chaperone for G protein-coupled receptors, regulating their biogenesis and exit from the ER.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism*
  • HEK293 Cells
  • Humans
  • Intracellular Membranes / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Protein Folding*
  • Protein Structure, Tertiary
  • Protein Transport / physiology
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled / biosynthesis*
  • Receptors, G-Protein-Coupled / genetics


  • ANKRD13C protein, human
  • Membrane Proteins
  • Molecular Chaperones
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled