Abstract
CaBP1-8 are neuronal Ca(2+)-binding proteins with similarity to calmodulin (CaM). Here we show that CaBP4 is specifically expressed in photoreceptors, where it is localized to synaptic terminals. The outer plexiform layer, which contains the photoreceptor synapses with secondary neurons, was thinner in the Cabp4(-/-) mice than in control mice. Cabp4(-/-) retinas also had ectopic synapses originating from rod bipolar and horizontal cells tha HJt extended into the outer nuclear layer. Responses of Cabp4(-/-) rod bipolars were reduced in sensitivity about 100-fold. Electroretinograms (ERGs) indicated a reduction in cone and rod synaptic function. The phenotype of Cabp4(-/-) mice shares similarities with that of incomplete congenital stationary night blindness (CSNB2) patients. CaBP4 directly associated with the C-terminal domain of the Ca(v)1.4 alpha(1)-subunit and shifted the activation of Ca(v)1.4 to hyperpolarized voltages in transfected cells. These observations indicate that CaBP4 is important for normal synaptic function, probably through regulation of Ca(2+) influx and neurotransmitter release in photoreceptor synaptic terminals.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence / genetics
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Animals
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Base Sequence / genetics
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Calcium / metabolism
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Calcium Channels / genetics
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Calcium Channels / metabolism*
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Calcium Channels, L-Type / genetics
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Calcium Channels, L-Type / metabolism*
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / isolation & purification
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Calcium-Binding Proteins / metabolism*
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Cell Line
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Choristoma / genetics
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Choristoma / metabolism
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Choristoma / pathology
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Humans
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Membrane Potentials / genetics
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / isolation & purification
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Nerve Tissue Proteins / metabolism*
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Neurotransmitter Agents / metabolism
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Night Blindness / genetics
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Night Blindness / metabolism
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Photoreceptor Cells / metabolism*
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Photoreceptor Cells / ultrastructure
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Retina / abnormalities*
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Retina / metabolism
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Retina / ultrastructure
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Synapses / metabolism*
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Synapses / ultrastructure
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Synaptic Transmission / genetics
Substances
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Cabp4 protein, mouse
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Cacna1f protein, mouse
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Calcium Channels
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Calcium Channels, L-Type
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Calcium-Binding Proteins
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DNA, Complementary
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Nerve Tissue Proteins
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Neurotransmitter Agents
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Calcium
Associated data
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GENBANK/AY039218
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GENBANK/AY039271
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GENBANK/AY048883
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RefSeq/XM_344981