Retinal ON bipolar cells express a new PCP2 splice variant that accelerates the light response

J Neurosci. 2008 Sep 3;28(36):8873-84. doi: 10.1523/JNEUROSCI.0812-08.2008.


PCP2, a member of the GoLoco domain-containing family, is present exclusively in cerebellar Purkinje cells and retinal ON bipolar cells. Its function in these tissues is unknown. Biochemical and expression system studies suggest that PCP2 is a guanine nucleotide dissociation inhibitor, although a guanine nucleotide exchange factor has also been suggested. Here, we studied the function of PCP2 in ON bipolar cells because their light response depends on Galpha(o1), which is known to interact with PCP2. We identified a new splice variant of PCP2 (Ret-PCP2) and localized it to rod bipolar and ON cone bipolar cells. Electroretinogram recordings from PCP2-null mice showed a normal a-wave but a slower falling phase of the b-wave (generated by the activity of ON bipolar cells) relative to the wild type. Whole-cell recordings from rod bipolar cells showed, both under Ames medium and after blocking GABA(A/C) and glycine receptors, that PCP2-null rod bipolar cells were more depolarized than wild-type cells with greater inward current when clamped to -60 mV. Also under both conditions, the rise time of the response to intense light was slower by 28% (Ames) and 44% (inhibitory blockers) in the null cells. Under Ames medium, we also observed >30% longer decay time in the PCP2-null rod bipolar cells. We conclude that PCP2 facilitates cation channels closure in the dark, shortens the rise time of the light response directly, and accelerates the decay time indirectly via the inhibitory network. These data can most easily be explained if PCP2 serves as a guanine nucleotide exchange factor.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA, Recombinant / genetics*
  • Electroretinography / methods
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Guanine Nucleotide Exchange Factors / deficiency
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Light*
  • Mass Spectrometry / methods
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Membrane Potentials / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuropeptides / deficiency
  • Neuropeptides / metabolism*
  • Patch-Clamp Techniques / methods
  • Photic Stimulation / methods
  • Picrotoxin / pharmacology
  • Reaction Time / genetics
  • Reaction Time / radiation effects
  • Retina / cytology
  • Retinal Bipolar Cells / physiology*
  • Retinal Bipolar Cells / radiation effects*
  • Strychnine / pharmacology
  • Transfection / methods


  • DNA, Recombinant
  • Guanine Nucleotide Exchange Factors
  • Neuropeptides
  • Pcp2 protein, mouse
  • enhanced green fluorescent protein
  • Picrotoxin
  • Green Fluorescent Proteins
  • Strychnine