Phosducin-like protein 1 is essential for G-protein assembly and signaling in retinal rod photoreceptors

J Neurosci. 2013 May 1;33(18):7941-51. doi: 10.1523/JNEUROSCI.5001-12.2013.

Abstract

G-protein β subunits perform essential neuronal functions as part of G-protein βγ and Gβ5-regulators of G-protein signaling (RGS) complexes. Both Gβγ and Gβ5-RGS are obligate dimers that are thought to require the assistance of the cytosolic chaperonin CCT and a cochaperone, phosducin-like protein 1 (PhLP1) for dimer formation. To test this hypothesis in vivo, we deleted the Phlp1 gene in mouse (Mus musculus) retinal rod photoreceptor cells and measured the effects on G-protein biogenesis and visual signal transduction. In the PhLP1-depleted rods, Gβγ dimer formation was decreased 50-fold, resulting in a >10-fold decrease in light sensitivity. Moreover, a 20-fold reduction in Gβ5 and RGS9-1 expression was also observed, causing a 15-fold delay in the shutoff of light responses. These findings conclusively demonstrate in vivo that PhLP1 is required for the folding and assembly of both Gβγ and Gβ5-RGS9.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biophysical Phenomena / genetics
  • Contrast Sensitivity / genetics
  • Dose-Response Relationship, Radiation
  • Electric Stimulation
  • Electroretinography
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • GTP-Binding Protein beta Subunits / metabolism
  • GTP-Binding Protein gamma Subunits / metabolism
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation / genetics
  • In Vitro Techniques
  • Light
  • Membrane Potentials / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Patch-Clamp Techniques
  • Photic Stimulation
  • RNA, Messenger / metabolism
  • Retina / cytology*
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology
  • Retinal Degeneration / physiopathology
  • Retinal Rod Photoreceptor Cells / metabolism*
  • Signal Transduction / physiology*
  • Visual Acuity / genetics

Substances

  • Eye Proteins
  • G-protein Beta gamma
  • GTP-Binding Protein beta Subunits
  • GTP-Binding Protein gamma Subunits
  • Membrane Proteins
  • R9AP protein, mouse
  • RNA, Messenger
  • phosducin-like orphan protein-1
  • GTP-Binding Proteins