The Journal of Neuroscience, November 14, 2007, 27(46):12743-12754; doi:10.1523/JNEUROSCI.4264-07.2007
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Cellular/Molecular
Phosphorylation of the Ca2+-Binding Protein CaBP4 by Protein Kinase C
in Photoreceptors
Amy Lee,1
Amber Jimenez,2
Guiying Cui,1 and
Françoise Haeseleer2
1Department of Pharmacology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322, and 2Department of Ophthalmology, University of Washington, Seattle, Washington 98195
Correspondence should be addressed to Françoise Haeseleer, University of Washington, Department of Ophthalmology, 1959 North East Pacific Street, Box 356485, Seattle, WA 98195. Email: fanfan{at}u.washington.edu
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 Cav1 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
(PKC
) at serine 37 both in vitro and in the retina and colocalizes with PKC
in photoreceptors. CaBP4 phosphorylation is greater in light-adapted than dark-adapted mouse retinas. In electrophysiological recordings of cells transfected with Cav1.3 and CaBP4, mutation of the serine 37 to alanine abolished the effect of CaBP4 in prolonging the Ca2+ current through Cav1.3 channel, whereas inactivating mutations in the CaBP4 Ca2+-binding sites strengthened Cav1.3 modulation. These findings demonstrate how light-stimulated changes in CaBP4 phosphorylation and Ca2+ binding may regulate presynaptic Ca2+ signals in photoreceptors.
Key words: CaBP4; Ca2+-binding proteins; phosphorylation; protein kinase C
; Ca2+ channel; photoreceptors
Received June 22, 2007;
accepted Oct. 9, 2007.
Correspondence should be addressed to Françoise Haeseleer, University of Washington, Department of Ophthalmology, 1959 North East Pacific Street, Box 356485, Seattle, WA 98195. Email: fanfan{at}u.washington.edu
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