Nitric oxide-mediated modulation of calcium/calmodulin-dependent protein kinase II

Song, Tao; Hatano, Naoya; Kambe, Toshie; Miyamoto, Yukio; Ihara, Hideshi; Yamamoto, Hideyuki; Sugimoto, Katsuyoshi; Kume, Kodai; Yamaguchi, Fuminori; Tokuda, Masaaki; Watanabe, Yasuo

doi:10.1042/bj20071195

Cited by 47 publications

(35 citation statements)

References 53 publications

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“…3E). Although the effect of nNOS and NO on GluA1-S831 phosphorylation might be the result of effects on PKC or CaMKII, this possibility is unlikely because S-nitrosylation of these two enzymes reduces their activity (19)(20)(21). Also, a role for guanylate cyclase in mediating the activating effects of NO on GluA1-S831 phosphorylation is unlikely because inhibition of cyclic guanylate kinase increases glycine-stimulated phosphorylation of GluA1-S831 (22).…”

Section: Resultsmentioning

confidence: 99%

S-nitrosylation of AMPA receptor GluA1 regulates phosphorylation, single-channel conductance, and endocytosis

Selvakumar

Jenkins

Hussain

et al. 2012

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

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NMDA receptor activation can elicit synaptic plasticity by augmenting conductance of the AMPA receptor GluA1 subsequent to phosphorylation at S831 by Ca 2+ -dependent kinases. NMDA receptor activation also regulates synaptic plasticity by causing endocytosis of AMPA receptor GluA1. We demonstrate a unique signaling cascade for these processes mediated by NMDA receptor-dependent NO formation and GluA1 S-nitrosylation. Thus, S-nitrosylation of GluA1 at C875 enhances S831 phosphorylation, facilitates the associated AMPA receptor conductance increase, and results in endocytosis by increasing receptor binding to the AP2 protein of the endocytotic machinery.A MPA receptors (AMPARs) are tetramers in their physiologic form, with GluA1 being one of the more important regulatory subunits (1). Synaptic plasticity frequently is mediated by activation of NMDA receptors (NMDARs), which can modulate surface expression and single-channel conductance of AMPARs during the early phase of long-term potentiation (LTP) (1, 2). Phosphorylation of S831 of GluA1 mediates such plasticity, as phosphorylation of this site increases during LTP (3, 4), and mutant mice overexpressing a phosphomimetic S831D mutation display enhanced AMPAR conductance and LTP (5, 6).Mechanisms whereby NMDAR transmission augments AMPAR conductance have been unclear. NMDAR activation leads to calcium entry, which stimulates catalytic activity of neuronal nitric oxide synthase (nNOS) (7,8). NO (nitric oxide) signals by activating guanylate cyclase, and by S-nitrosylating cysteines of many target proteins (9, 10). NO regulates AMPARs by targeting AMPARinteracting proteins that determine receptor surface expression. Thus, physiologic S-nitrosylation of NSF (N-ethylmaleimide sensitive factor) elicits enhanced surface expression of GluA2 (11). Transmembrane AMPAR regulatory proteins are prominent auxiliary proteins for AMPARs, with stargazin being the best characterized (12). NMDAR transmission triggers S-nitrosylation of stargazin, which increases surface expression of GluA1 (13).The surface expression of AMPARs that determines synaptic plasticity is regulated by endocytosis because inhibitors of endocytosis block AMPAR removal from the plasma membrane, resulting in increased surface expression of AMPARs and long term depression (LTD) (14). Although NO has been implicated in regulation of protein endocytosis (15), its role in regulating AMPAR endocytosis is unknown.In the present study, we show that GluA1 is physiologically S-nitrosylated under basal conditions, with increased nitrosylation upon NMDAR stimulation. Moreover, the NMDAR-dependent phosphorylation of GluA1-S831 is regulated by endogenous NO, which acts by S-nitrosylating GluA1-C875. These events regulate single-channel conductance of GluA1, as the increase of such conductance by phosphorylation is markedly slowed in GluA1-C875S mutants. Endocytosis of AMPAR also is regulated by nitrosylation of GluA1-C875, because the C875S mutant of GluA1 reduces AMPAR endocytosis in neuronal cells and decreases binding ...

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Section: Resultsmentioning

confidence: 99%

S-nitrosylation of AMPA receptor GluA1 regulates phosphorylation, single-channel conductance, and endocytosis

Selvakumar

Jenkins

Hussain

et al. 2012

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

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“…In this regard, it is noteworthy that excitatory glutamatergic neurotransmission reduces Cdk5 activity through enhancing the proteasome-dependent degradation of p35 (Wei et al, 2005). Interestingly, glutamate stimulation of neurons is able to trigger neuronal nitric oxide synthase activation, and results in protein S-nitrosylation (Bredt and Snyder, 1994;Song et al, 2008), making glutamate a likely candidate that can inhibit Cdk5 activity through S-nitrosylation. Thus, it is possible that S-nitrosylation of Cdk5 also contributes, at least in part, to the reduced kinase activity upon glutamate-induced NMDA receptor activation.…”

Section: Discussionmentioning

confidence: 99%

“…Under dynamic regulation by the NO signaling pathway, S-nitrosylation of a protein can modify its activity or function. For example, it has been reported that S-nitrosylation is important for regulating the catalytic activity of various kinases, including G protein-coupled receptor kinase 2, Akt/protein kinase B, Src kinase, inhibitory B kinase, or Ca 2ϩ /calmodulin-dependent protein kinase II (Reynaert et al, 2004;Yasukawa et al, 2005;Whalen et al, 2007;Song et al, 2008;Rahman et al, 2010). Whereas NO signaling pathway is one of the key regulators in a wide array of neurodevelopmental processes, including neuronal differentiation, neuronal survival, and synaptic plasticity (Guix et al, 2005), deregulation of this pathway has been implicated in the pathogenesis of neurological disorders such as Alzheimer's disease, Parkinson's disease, and stroke (Chung, 2006).…”

Section: Introductionmentioning

confidence: 99%

S-Nitrosylation of Cyclin-Dependent Kinase 5 (Cdk5) Regulates Its Kinase Activity and Dendrite Growth During Neuronal Development

Zhang¹,

Yu²,

Tsang³

et al. 2010

J. Neurosci.

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Precise regulation of cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family, is critical for proper neuronal development and functions. Cdk5 is activated through its association with the neuron-specific activator p35 or p39. Nonetheless, how its kinase activity is regulated in neurons is not well understood. In this study, we found that Cdk5 activity is regulated by S-nitrosylation, a post-translational modification of protein that affects a plethora of neuronal functions. S-nitrosylation of Cdk5 occurs at Cys83, which is one of the critical amino acids within the ATP-binding pocket of the kinase. Upon S-nitrosylation, Cdk5 exhibits reduced kinase activity, whereas mutation of Cys83 to Ala on Cdk5 renders the kinase refractory to such inhibition. Importantly, S-nitrosylated Cdk5 can be detected in the mouse brain, and blocking the S-nitrosylation of Cdk5 in cultured hippocampal neurons enhances dendritic growth and branching. Together, our findings reveal an important role of S-nitrosylation in regulating Cdk5 kinase activity and dendrite growth in neurons during development.

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“…A previous study showed that NO inhibits CaMKII activity through S-nitrosylation at C6 (30). To address this apparently conflicting finding, CaMKII was exposed to NO for varying periods of time (Fig.…”

Section: Prolonged Exposure To Nitric Oxide Reduces Camkii Activity-mentioning

confidence: 99%

Nitric Oxide Induces Ca2+-independent Activity of the Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII)

Coultrap

Bayer

2014

Journal of Biological Chemistry

146

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Background: Ca 2ϩ -independent autonomous CaMKII activity and nitric oxide (NO) signaling regulate neuronal function and death. Results: NO generated autonomous CaMKII activity by Ca 2ϩ /CaM-dependent S-nitrosylation, and CaMKII inhibition protected from NO-induced neuronal cell death. Conclusion: NO-mediated regulation of CaMKII contributes to its pathological functions. Significance: S-Nitrosylation is a novel path to CaMKII autonomy that connects Ca 2ϩ -and NO signaling.

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Nitric oxide-mediated modulation of calcium/calmodulin-dependent protein kinase II

Cited by 47 publications

References 53 publications

S-nitrosylation of AMPA receptor GluA1 regulates phosphorylation, single-channel conductance, and endocytosis

S-nitrosylation of AMPA receptor GluA1 regulates phosphorylation, single-channel conductance, and endocytosis

S-Nitrosylation of Cyclin-Dependent Kinase 5 (Cdk5) Regulates Its Kinase Activity and Dendrite Growth During Neuronal Development

Nitric Oxide Induces Ca2+-independent Activity of the Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII)

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