Functional consequences of expression of the neuron-specific, protein kinase C substrate RC3 (neurogranin) in Xenopus oocytes

Cohen, Rochelle S.; Margulies, Jody E.; Coulter, Phillip M.; Watson, Joseph B.

doi:10.1016/0006-8993(93)90758-f

Cited by 39 publications

(26 citation statements)

References 42 publications

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“…In this scenario, Ng phosphorylation would act as a ''slider'' that shifts the synaptic frequency-response curve to the left (enhanced postsynaptic sensitivity) or to the right (decreased postsynaptic sensitivity) depending on the level of phosphorylation, as proposed earlier (86). Finally, there are several studies suggesting that phospho-Ng has a signaling role ''per se'' based on the evidence obtained in Xenopus oocytes injected with Ng mRNA (96,97). These reports showed that Ng is able to directly stimulate G-protein coupled second messenger pathways only when phosphorylated by PKC, thus assigning a protagonist role to phospho-Ng as a signaling enhancer in addition to its role as intracellular CaM buffer.…”

Section: Mechanisms and Functionmentioning

confidence: 92%

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: Mechanisms and Functionmentioning

confidence: 92%

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

2010

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“…The CaM-binding affinity of Ng is attenuated by phosphorylation with protein kinase C (PKC) and by oxidation with nitric oxide (NO) (4-7); both modifications have the potential to modulate neuronal free Ca 2ϩ and CaM levels. The phosphorylated Ng also stimulates the G-protein-coupled phosphoinositide second messenger pathways that trigger the mobilization of Ca 2ϩ from intracellular stores (8). PKC is the only known Ng kinase in vitro (5), and deletion of PKC ␥ gene in mice negates both the glutamate-and depolarization-mediated phosphorylation of Ng (9).…”

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confidence: 99%

Involvement of neurogranin in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: A study with knockout mice

Pak

Huang

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

239

229

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Neurogranin͞RC3 is a neural-specific Ca 2؉ -sensitive calmodulin (CaM)-binding protein whose CaM-binding affinity is modulated by phosphorylation and oxidation. Here we show that deletion of the Ng gene in mice did not result in obvious developmental or neuroanatomical abnormalities but caused an impairment of spatial learning and changes in hippocampal short-and long-term plasticity (paired-pulse depression, synaptic fatigue, long-term potentiation induction). These deficits were accompanied by a decreased basal level of the activated Ca 2؉ ͞CaM-dependent kinase II (CaMKII) (Ϸ60% of wild type). Furthermore, hippocampal slices of the mutant mice displayed a reduced ability to generate activated CaMKII after stimulation of protein phosphorylation and oxidation by treatments with okadaic acid and sodium nitroprusside, respectively. These results indicate a central role of Ng in the regulation of CaMKII activity with decisive influences on synaptic plasticity and spatial learning.

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“…On the other hand, like phosphorylated B-50, phosphorylated neurogranin itself may also be of significance to the maintenance of LTP. In this respect the suggestion that phosphorylated neurogranin may be involved in regulating the releases Ca 2+ from intracellular stores [20] is worth considering.…”

Section: Discussionmentioning

confidence: 99%

“…Intracellular injection of PKC (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31), a peptide fragment representing the pseudosubstrate region of the regulatory domain of PKC, prevented the maintenance of LTP in the injected cell whereas the neighbouring cells showed normal LTP [48]. These results indicate that postsynaptic PKC is involved in the maintenance of LTP.…”

Section: Ltp and Pkcmentioning

confidence: 98%

“…Recently, Watson and coworkers proposed that PKC phosphorylated neurogranin may play a role in calcium homeostasis in dendrites of forebrain neurons by modulating the inositol 1,4,5-triphosphate and diacylglycerol second messenger pathways [20]. Alternatively, neurogranin may serve as local calmodulin store, releasing calmodulin in response to PKC-mediated phosphorylation and a rise in intracellular calcium levels, thus activating postsynaptic Ca 2 ÷/calmodulin dependent signal transduction pathways.…”

Section: Neurograninmentioning

confidence: 99%

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Long-term potentiation and synaptic protein phosphorylation

Pasinelli

Ramakers

Urban

et al. 1995

Behavioural Brain Research

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Long-term potentiation (LTP) is a well known experimental model for studying the activity-dependent enhancement of synaptic plasticity, and because of its long duration and its associative properties, it has been proposed as a system to investigate the molecular mechanisms of memory formation. At present, there are several lines of evidence that indicate that pre-and postsynaptic kinases and their specific substrates are involved in molecular mechanisms underlying LTP. Many studies focus on the involvement of protein kinase C (PKC). One way to investigate the role of PKC in long-term potentiation is to determine the degree of phosphorylation of its substrates after in situ phosphorylation in hippocampal slices. Two possible targets are the presynaptic membrane-associated protein B-50 (a.k.a. GAP 43, neuromodulin and F1), which has been implicated in different forms of synaptical plasticity in the brain such as neurite outgrowth, hippocampal LTP and neurotransmitter release, and the postsynaptic protein neurogranin (a.k.a. RC3, BICKS and p17) which function remains to be determined. This review will focus on the protein kinase C activity in pre-and postsynaptic compartment during the early phase of LTP and the possible involvement of its substrates B-50 and neurogranin.

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Functional consequences of expression of the neuron-specific, protein kinase C substrate RC3 (neurogranin) in Xenopus oocytes

Cited by 39 publications

References 42 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

Involvement of neurogranin in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: A study with knockout mice

Long-term potentiation and synaptic protein phosphorylation

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