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

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.