Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling

PLoS One. 2015 Feb 6;10(2):e0117129. doi: 10.1371/journal.pone.0117129. eCollection 2015.


G protein β subunits (Gβ) play essential roles in phototransduction as part of G protein βγ (Gβγ) and regulator of G protein signaling 9 (RGS9)-Gβ5 heterodimers. Both are obligate dimers that rely on the cytosolic chaperone CCT and its co-chaperone PhLP1 to form complexes from their nascent polypeptides. The importance of PhLP1 in the assembly process was recently demonstrated in vivo in a retinal rod-specific deletion of the Phlp1 gene. To test whether this is a general mechanism that also applies to other cell types, we disrupted the Phlp1 gene specifically in mouse cones and measured the effects on G protein expression and cone visual signal transduction. In PhLP1-deficient cones, expression of cone transducin (Gt2) and RGS9-Gβ5 subunits was dramatically reduced, resulting in a 27-fold decrease in sensitivity and a 38-fold delay in cone photoresponse recovery. These results demonstrate the essential role of PhLP1 in cone G protein complex formation. Our findings reveal a common mechanism of Gβγ and RGS9-Gβ5 assembly in rods and cones, highlighting the importance of PhLP1 and CCT-mediated Gβ complex formation in G protein signaling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • GTP-Binding Protein beta Subunits / biosynthesis*
  • GTP-Binding Protein beta Subunits / genetics
  • GTP-Binding Protein gamma Subunits / biosynthesis*
  • GTP-Binding Protein gamma Subunits / genetics
  • Gene Expression Regulation, Enzymologic / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Molecular Chaperones
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Multimerization / physiology*
  • Retinal Cone Photoreceptor Cells / metabolism*
  • Signal Transduction / physiology*
  • Transducin / biosynthesis*
  • Transducin / genetics


  • Carrier Proteins
  • GTP-Binding Protein beta Subunits
  • GTP-Binding Protein gamma Subunits
  • Membrane Proteins
  • Molecular Chaperones
  • Nerve Tissue Proteins
  • Pdcl protein, mouse
  • R9AP protein, mouse
  • Transducin