Phosphorylation of the Ca2+-binding protein CaBP4 by protein kinase C zeta in photoreceptors.
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.
Lee
Amy
A
Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Jimenez
Amber
A
Cui
Guiying
G
Haeseleer
Françoise
F
D000221:Adaptation, Ocular / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics / Q000528:radiation effects; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics* / Q000528:radiation effects; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000528:radiation effects; D010775:Photic Stimulation; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism; D014785:Vision, Ocular / Q000235:genetics / Q000528:radiation effects
C494133:Cabp4 protein, mouse; C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; D012694:Serine; C488488:protein kinase C zeta II, mouse; D011493:Protein Kinase C; D002118:Calcium