Localization of RC3 (neurogranin) in rat brain subcellular fractions

Watson, Joseph B.; Szijan, Irene; Coulter, Phillip M.

doi:10.1016/0169-328x(94)90017-5

Cited by 49 publications

(42 citation statements)

References 28 publications

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“…Although some studies had reported the presence of Ng in neuronal nuclei (9,71), other studies were not able to find nuclear Ng (73,75). Recent work reconciles these results showing that detection of nucleoplasmic Ng is highly dependent on the experimental procedure employed (80).…”

Section: Subcellular Localizationmentioning

confidence: 51%

“…These granules, which gave to Ng its name, are often attached or in close proximity to mitochondria, the endoplasmic reticulum (ER), and the trans-Golgi network (73). The association of Ng to membranes was first suggested by in vitro experiments showing Ng binding to acidic phospholipids (74) and, later, by the identification of Ng in microsomal and synaptosomal fractions of the rat brain (75). More recently, Ng association with cellular membranes has been proposed to be mediated by its direct interaction with phosphatidic acid (PA) (76).…”

Section: Subcellular Localizationmentioning

confidence: 99%

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Neurogranin, a link between calcium/calmodulin and protein kinase C signaling in synaptic plasticity

2010

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SummaryNeurogranin (Ng) (also named RC3, p17 or BICKS) is a small protein originally identified in rat brain and abundantly expressed in several telencephalic areas, such as the cerebral cortex, hippocampus, amygdala, and striatum. In neurons, it is found concentrated at dendritic spines where it participates in synaptic signaling events through the regulation of calmodulin (CaM) availability. Ng features an IQ motif that mediates its interaction with CaM and phosphatidic acid (PA) and that is phosphorylated by protein kinase C (PKC) at serine 36 (Ser36). Ser36-phosphorylated Ng is unable to bind either CaM or PA. Ng knockout mice display an apparently normal phenotype; however, they show severe deficits in spatial and emotional learning and a decrease in LTP induction, mostly due to the attenuation of the signaling that depends on calcium/CaM kinase II (CaMKII), PKC, and protein kinase A (PKA) activation. The present review is an update on the most relevant information about Ng expression, localization, interactions, and modifications as well as on its role in synaptic plasticity. IUBMBIUBMB Life, 62(8): 597-606, 2010

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Section: Subcellular Localizationmentioning

confidence: 51%

Section: Subcellular Localizationmentioning

confidence: 99%

Neurogranin, a link between calcium/calmodulin and protein kinase C signaling in synaptic plasticity

2010

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“…1 is a brain-specific, Ca 2ϩ -sensitive calmodulin (CaM)-binding phosphoprotein, and is highly expressed in the neuronal cell bodies and dendrites within the hippocampus, neocortex, amygdala, and striatum (1)(2)(3)(4)(5). Ng is a specific substrate of protein kinase C (PKC), and it can also be modified by nitric oxide and other oxidants to form intramolecular disulfide (6 -9).…”

Section: Neurogranin (Ng)mentioning

confidence: 99%

Attenuation of Protein Kinase C and cAMP-dependent Protein Kinase Signal Transduction in the Neurogranin Knockout Mouse

Huang

et al. 2002

Journal of Biological Chemistry

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Neurogranin (Ng) is a brain-specific, postsynaptically located protein kinase C (PKC) substrate, highly expressed in the cortex, hippocampus, striatum, and amygdala. This protein is a Ca 2؉ -sensitive calmodulin (CaM)-binding protein whose CaM-binding affinity is modulated by phosphorylation and oxidation. To investigate the role of Ng in neural function, a strain of Ng knockout mouse (KO) was generated. Previously we reported (Pak, J. H., Huang, F. L., Li, J., Balschun, D., Reymann, K. G., Chiang, C., Westphal, H., and Huang, K.-P. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 11232-11237) that these KO mice displayed no obvious neuroanatomical abnormality, but exhibited deficits in learning and memory and activation of Ca 2؉ /CaM-dependent protein kinase II. In this report, we analyzed several downstream phosphorylation targets in phorbol 12-myristate 13-acetate-and forskolin-treated hippocampal slices from wild type (WT) and KO mice. Phorbol 12-myristate 13-acetate caused phosphorylation of Ng in WT mice and promoted the translocation of PKC from the cytosolic to the particulate fractions of both the WT and KO mice, albeit to a lesser extent in the latter. Phosphorylation of downstream targets, including mitogenactivated protein kinases, 90-kDa ribosomal S6 kinase, and the cAMP response element binding protein (CREB) was significantly attenuated in KO mice. Stimulation of hippocampal slices with forskolin also caused greater stimulation of protein kinase A (PKA) in the WT as compared with those of the KO mice. Again, phosphorylation of the downstream targets of PKA was attenuated in the KO mice. These results suggest that Ng plays a pivotal role in regulating both PKC-and PKA-mediated signaling pathways, and that the deficits in learning and memory of spatial tasks detected in the KO mice may be the result of defects in the signaling pathways leading to the phosphorylation of CREB. Neurogranin (Ng)1 is a brain-specific, Ca 2ϩ -sensitive calmodulin (CaM)-binding phosphoprotein, and is highly expressed in the neuronal cell bodies and dendrites within the hippocampus, neocortex, amygdala, and striatum (1-5). Ng is a specific substrate of protein kinase C (PKC), and it can also be modified by nitric oxide and other oxidants to form intramolecular disulfide (6 -9). Both the phosphorylation and oxidation of Ng attenuate its binding affinity for CaM (7, 9 -11). To investigate the role of Ng in neural function, a strain of Ng knockout mouse (KO) was generated (12). These mutant mice displayed no obvious neuroanatomical abnormality; however, they exhibited deficits in learning the spatial tasks when tested with Morris water maze. In addition, Ca 2ϩ /CaM-dependent protein kinase II (CaMKII) in the hippocampal slices of these KO mice is less readily autophosphorylated as compared with those of the wild type (WT) mice upon treatments that enhance Ng phosphorylation and oxidation.Induction of hippocampal long term potentiation (LTP, an experimental model of learning and memory) is well recognized to be initiated by the stimu...

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“…Neurogranin (RC3, BICKS) is a postnatal expressed brainspecific protein that is localized postsynaptically in neuronal cell bodies and dendrites of the cerebral cortex, hippocampus, and striatum (1)(2)(3)(4)(5). It was first identified by subtractive hybridization in a screen for mRNAs enriched in rat forebrain and was independently purified from brain as a protein kinase C (PKC) 1 substrate (6 -9).…”

mentioning

confidence: 99%

Interactions between Neurogranin and Calmodulin in Vivo

Prichard

Deloulme

Storm

1999

Journal of Biological Chemistry

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Neurogranin is a neural-specific, calmodulin (CaM)-binding protein that is phosphorylated by protein kinase C (PKC) within its IQ domain at serine 36. Since CaM binds to neurogranin through the IQ domain, PKC phosphorylation and CaM binding are mutually exclusive. Consequently, we hypothesize that neurogranin may function to concentrate CaM at specific sites in neurons and release free CaM in response to increased Ca 2؉ and PKC activation. However, it has not been established that neurogranin interacts with CaM in vivo. In this study, we examined this question using yeast two-hybrid methodology. We also searched for additional proteins that might interact with neurogranin by screening brain cDNA libraries. Our data illustrate that CaM binds to neurogranin in vivo and that CaM is the only neurogranin-interacting protein isolated from brain cDNA libraries. Single amino acid mutagenesis indicated that residues within the IQ domain are important for CaM binding to neurogranin in vivo. The Ile-33 3 Gln point mutant completely inhibited and Arg-38 3 Gln and Ser-36 3 Asp point mutants reduced neurogranin/CaM interactions. These data demonstrate that CaM is the major protein that interacts with neurogranin in vivo and support the hypothesis that phosphorylation of neurogranin at Ser-36 regulates its binding to CaM.

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Localization of RC3 (neurogranin) in rat brain subcellular fractions

Cited by 49 publications

References 28 publications

Neurogranin, a link between calcium/calmodulin and protein kinase C signaling in synaptic plasticity

Neurogranin, a link between calcium/calmodulin and protein kinase C signaling in synaptic plasticity

Attenuation of Protein Kinase C and cAMP-dependent Protein Kinase Signal Transduction in the Neurogranin Knockout Mouse

Interactions between Neurogranin and Calmodulin in Vivo

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