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• W2016000613 endingPage "1214" @default.
• W2016000613 startingPage "1214" @default.
• W2016000613 abstract "Purpose.: CaBP4 is a neuronal Ca2+-binding protein that is expressed in the retina and in the cochlea, and is essential for normal photoreceptor synaptic function. CaBP4 is phosphorylated by protein kinase C zeta (PKCζ) in the retina at serine 37, which affects its interaction with and modulation of voltage-gated Cav1 Ca2+ channels. In this study, we investigated the potential role and functional significance of protein phosphatase 2A (PP2A) in CaBP4 dephosphorylation. Methods.: The effect of protein phosphatase inhibitors, light, and overexpression of PP2A subunits on CaBP4 dephosphorylation was measured in in vitro assays. Pull-down experiments using retinal or transfected HEK293 cell lysates were used to investigate the association between CaBP4 and PP2A subunits. Electrophysiologic recordings of cotransfected HEK293 cells were performed to analyze the effect of CaBP4 dephosphorylation in modulating Cav1.3 currents. Results.: PP2A inhibitors, okadaic acid (OA), and fostriecin, but not PP1 selective inhibitors, NIPP-1, and inhibitor 2, block CaBP4 dephosphorylation in retinal lysates. Increased phosphatase activity in light-dependent conditions reverses phosphorylation of CaBP4 by PKCζ. In HEK293 cells, overexpression of PP2A enhances the rate of dephosphorylation of CaBP4. In addition, inhibition of protein phosphatase activity by OA increases CaBP4 phosphorylation and potentiates the modulatory effect of CaBP4 on Cav1.3 Ca2+ channels in HEK293T cells. Conclusions.: This study provides evidence that CaBP4 is dephosphorylated by PP2A in the retina. Our findings reveal a novel role for protein phosphatases in regulating CaBP4 function in the retina, which may fine tune presynaptic Ca2+ signals at the photoreceptor synapse." @default.
• W2016000613 created "2016-06-24" @default.
• W2016000613 creator A5030256643 @default.
• W2016000613 creator A5042328864 @default.
• W2016000613 creator A5073126046 @default.
• W2016000613 creator A5078900835 @default.
• W2016000613 date "2013-02-12" @default.
• W2016000613 modified "2023-09-26" @default.
• W2016000613 title "Protein Phosphatase 2A Dephosphorylates CaBP4 and Regulates CaBP4 Function" @default.
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• W2016000613 doi "https://doi.org/10.1167/iovs.12-11319" @default.
• W2016000613 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3575156" @default.
• W2016000613 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23341017" @default.
• W2016000613 hasPublicationYear "2013" @default.
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