A Mechanism for Tunable Autoinhibition in the Structure of a Human Ca2+/Calmodulin- Dependent Kinase II Holoenzyme

Chao, Luke H.; Stratton, Margaret M.; Lee, Il‐Hyung; Rosenberg, Oren S.; Levitz, Joshua; Mandell, Daniel J.; Kortemme, Tanja; Groves, Jay T.; Schulman, Howard; Kuriyan, John

doi:10.1016/j.cell.2011.10.013

Cited by 64 publications

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“…Model of CaMKII structure and regulation. A, CaMKII forms 12meric holoenzymes via C-terminal association domains, with the kinase domains radiating outward (1,2). Each kinase subunit is activated separately by direct binding of Ca 2ϩ /CaM, which can also induce intra-holoenzyme inter-subunit Thr-286 autophosphorylation (9).…”

Section: Methodsmentioning

confidence: 99%

“…Each kinase subunit is activated separately by direct binding of Ca 2ϩ /CaM, which can also induce intra-holoenzyme inter-subunit Thr-286 autophosphorylation (9). B, structure of the CaMKII kinase (space-fill) and regulatory (ribbon) domains (2). In the basal inactive state, the substrate binding S-site (orange) is blocked by the regulatory domain, which is held in place in part by interactions with the neighboring T-site (yellow).…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

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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“…Atomic structures of holoenzymes from Caenorhabditis elegans (Rosenberg et al 2005) and human (Rellos et al 2010;Chao et al 2011) revealed that the 12 subunits are arranged in two closely apposed rings (Fig. 3).…”

Section: Camkiimentioning

confidence: 99%

“…Binding of calcium-CaM to one of the subunits in a dimer activates that subunit and frees its partner, increasing its availability to bind calcium-CaM. The magnitude of the resulting cooperativity for binding of calcium-CaM depends on the nature of the subunit dimer interface and the length of the linker region between the catalytic and association domains (Chao et al 2010(Chao et al , 2011. Thus, the sensitivity of CaMKII to activation by calcium is highly tuned, differing among different species and among individual isoforms in the same species.…”

Section: Camkiimentioning

confidence: 99%

Synaptic Signaling in Learning and Memory

Kennedy

2013

Cold Spring Harb Perspect Biol

134

108

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SUMMARYLearning and memory require the formation of new neural networks in the brain. A key mechanism underlying this process is synaptic plasticity at excitatory synapses, which connect neurons into networks. Excitatory synaptic transmission happens when glutamate, the excitatory neurotransmitter, activates receptors on the postsynaptic neuron. Synaptic plasticity is a higher-level process in which the strength of excitatory synapses is altered in response to the pattern of activity at the synapse. It is initiated in the postsynaptic compartment, where the precise pattern of influx of calcium through activated glutamate receptors leads either to the addition of new receptors and enlargement of the synapse (long-term potentiation) or the removal of receptors and shrinkage of the synapse (long-term depression). Calcium/calmodulin-regulated enzymes and small GTPases collaborate to control this highly tuned mechanism.

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“…In basal conditions, the catalytic domain, responsible for the phosphotransferase reaction, is inhibited by the autoinhibitory domain of the same subunit, which is acting like a gate Lisman et al 2012). When the calcium concentration rises, the calcium/ calmodulin complex subsequently formed can bind to the autoinhibitory domain, enabling the gate to open and thus the substrate to access its binding site (Morris and Török 2001;Hudmon and Schulman 2002;Rellos et al 2010;Chao et al 2011). Another consequence of this opening is the exposure of a particular amino acid, Thr286, on the a subunit (Thr287 for the b subunit), located in the autoinhibitory domain.…”

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confidence: 99%

Long-term potentiation can be induced in the CA1 region of hippocampus in the absence of αCaMKII T286-autophosphorylation

2014

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a-calcium/calmodulin-dependent protein kinase (aCaMKII) T286-autophosphorylation provides a short-term molecular memory that was thought to be required for LTP and for learning and memory. However, it has been shown that learning can occur in aCaMKII-T286A mutant mice after a massed training protocol. This raises the question of whether there might be a form of LTP in these mice that can occur without T286 autophosphorylation. In this study, we confirmed that in CA1 pyramidal cells, LTP induced in acute hippocampal slices, after a recovery period in an interface chamber, is strictly dependent on postsynaptic aCaMKII autophosphorylation. However, we demonstrated that aCaMKII-autophosphorylation-independent plasticity can occur in the hippocampus but at the expense of synaptic specificity. This nonspecific LTP was observed in mutant and wild-type mice after a recovery period in a submersion chamber and was independent of NMDA receptors. Moreover, when slices prepared from mutant mice were preincubated during 2 h with rapamycin, high-frequency trains induced a synapse-specific LTP which was added to the nonspecific LTP. This specific LTP was related to an increase in the duration and the amplitude of NMDA receptor-mediated response induced by rapamycin.The formation of memories is believed to be achieved through strengthening of synaptic communication between two simultaneously active neurons, a phenomenon called long-term potentiation (LTP). For several years, numerous studies have sought to better understand the molecular mechanisms of synaptic plasticity and LTP, and in particular the role of calcium-calmodulin-dependent protein kinase II (CaMKII), one of the most important postsynaptic components in glutamatergic synapses. Indeed, CaMKII is both necessary and sufficient for LTP induction. The application of CaMKII inhibitors, such as KN-62 or KN-93, or genetic disruption of the CaMKII gene can block LTP (Malinow et al. 1989;Otmakhov et al. 1997;Hinds et al. 1998;Yamagata et al. 2009). Conversely, the injection or viral expression of a constitutively active form of CaMKII leads to the improvement of spatial memory (Poulsen et al. 2007), in enhancement of AMPAR-mediated synaptic transmission and occludes further induction of LTP (McGladeMcCulloh et al. 1993;Pettit et al. 1994;Lledo et al. 1995). This enhancement in AMPAR conductance has been proposed to occur through an increase in synaptic trafficking of GluA1 subunits, as well as phosphorylation of GluA1 at Ser831 (Shi et al. 1999;Hayashi et al. 2000;Broutman and Baudry 2001;Esteban et al. 2003;Oh et al. 2006). Besides its role in synaptic transmission, CaMKII is also involved in the structural plasticity of spines, and more specifically in activity-dependent spine growth following NMDAR activation (Okamoto et al. 2009;Pi et al. 2010). Moreover, it seems that CaMKII-dependent processes involved in hippocampal LTP in CA1 synapses are quite general since the kinase also affects in vivo plasticity in different brain regions (Wu and Cline 1998;Zou and Cline 1999). ...

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A Mechanism for Tunable Autoinhibition in the Structure of a Human Ca2+/Calmodulin- Dependent Kinase II Holoenzyme

Cited by 64 publications

References 0 publications

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

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

Synaptic Signaling in Learning and Memory

Long-term potentiation can be induced in the CA1 region of hippocampus in the absence of αCaMKII T286-autophosphorylation

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