Phosphorylation of the Ca2+-binding protein CaBP4 by protein kinase C zeta in photoreceptors

J Neurosci. 2007 Nov 14;27(46):12743-54. doi: 10.1523/JNEUROSCI.4264-07.2007.

Abstract

CaBP4 is a calmodulin-like neuronal calcium-binding protein that is crucial for the development and/or maintenance of the cone and rod photoreceptor synapse. Previously, we showed that CaBP4 directly regulates Ca(v)1 L-type Ca2+ channels, which are essential for normal photoreceptor synaptic transmission. Here, we show that the function of CaBP4 is regulated by phosphorylation. CaBP4 is phosphorylated by protein kinase C zeta (PKCzeta) at serine 37 both in vitro and in the retina and colocalizes with PKCzeta in photoreceptors. CaBP4 phosphorylation is greater in light-adapted than dark-adapted mouse retinas. In electrophysiological recordings of cells transfected with Ca(v)1.3 and CaBP4, mutation of the serine 37 to alanine abolished the effect of CaBP4 in prolonging the Ca2+ current through Ca(v)1.3 channel, whereas inactivating mutations in the CaBP4 Ca2+-binding sites strengthened Ca(v)1.3 modulation. These findings demonstrate how light-stimulated changes in CaBP4 phosphorylation and Ca2+ binding may regulate presynaptic Ca2+ signals in photoreceptors.

Publication types

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

MeSH terms

  • Adaptation, Ocular / genetics
  • Amino Acid Substitution / genetics
  • Animals
  • Binding Sites / genetics
  • Binding Sites / radiation effects
  • Calcium / metabolism
  • Calcium Channels, L-Type / metabolism
  • Calcium Signaling / genetics*
  • Calcium Signaling / radiation effects
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Phosphorylation / radiation effects
  • Photic Stimulation
  • Photoreceptor Cells, Vertebrate / cytology
  • Photoreceptor Cells, Vertebrate / metabolism*
  • Photoreceptor Cells, Vertebrate / radiation effects
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Retina / cytology
  • Retina / metabolism*
  • Serine / genetics
  • Serine / metabolism
  • Vision, Ocular / genetics
  • Vision, Ocular / radiation effects

Substances

  • Cabp4 protein, mouse
  • Cacna1d protein, mouse
  • Calcium Channels, L-Type
  • Calcium-Binding Proteins
  • Nerve Tissue Proteins
  • Serine
  • protein kinase C zeta II, mouse
  • Protein Kinase C
  • Calcium