Metabolic Regulation of CaMKII Protein and Caspases in Xenopus laevis Egg Extracts

McCoy, Francis; Darbandi, Rashid; Chen, Si Ing; Eckard, Laura; Dodd, Keela; Jones, Kelly A.; Baucum, Anthony J.; Gibbons, Jennifer A.; Lin, Sue Hwa; Colbran, Roger J.; Nutt, Leta K.

doi:10.1074/jbc.m112.437186

Cited by 9 publications

(7 citation statements)

References 34 publications

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“…3C), similar to G6P. The pattern of the three bands recognized by the phospho-Thr-286/287 antibody is similar to the pattern previously detected using a pan-CaMKII antibody that recognizes the α, β, γ, and δ isoforms of CaMKII (McCoy et al 2013). Depletion of CaMKII from extracts using CAM-Sepharose inhibited the CoA-dependent phosphorylation of caspase-2 (Fig.…”

Section: Resultssupporting

confidence: 80%

“…The biochemistry detailing the requirement for CaMKII in egg activation was first demonstrated using the Xenopus egg. Our previous data further demonstrate that in X. laevis oocytes CaMKII is a hetero-dodecamer, composed of multiple isoforms (McCoy et al 2013). …”

Section: Introductionsupporting

confidence: 58%

“…We have previously identified a novel link between G6P-induced pentose phosphate pathway generation of NADPH and the cell death machinery (Nutt et al 2005; Nutt et al 2009; McCoy et al 2013). We postulated that G6P/NADPH induced an active signaling system to keep these cells alive and that the default pathway, when key metabolites cannot be maintained, is cell death.…”

Section: Discussionmentioning

confidence: 99%

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Metabolic Activation of CaMKII by Coenzyme A

et al. 2013

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SUMMARY Active metabolism regulates oocyte cell death via calcium/calmodulin-dependent protein kinase II (CaMKII) mediated phosphorylation of caspase-2, but the link between metabolic activity and CaMKII is poorly understood. Here we identify coenzyme A (CoA) as the key metabolic signal that inhibits Xenopus laevis oocyte apoptosis, in a novel mechanism of CaMKII activation. We found that CoA directly binds to the CaMKII regulatory domain in the absence of Ca2+ to activate CaMKII in a calmodulin-dependent manner. Furthermore, we show that CoA inhibits apoptosis not only in X. laevis oocytes, but also in Murine oocytes. These findings uncover a novel mechanism of CaMKII regulation by metabolism and further highlight the importance of metabolism in preserving oocyte viability.

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Section: Resultssupporting

confidence: 80%

Section: Introductionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

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Metabolic Activation of CaMKII by Coenzyme A

et al. 2013

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“…1B). As also reported, CaMKII can physically bind the caspase-2 prodomain, which is stimulated by G6P treatment (25). Interestingly, an up-regulation of Thr 286 phosphorylation was also observed in human 293T cells after glucose starvation and resupplementation (Fig.…”

Section: Resultssupporting

confidence: 53%

“…Studies of CaMKII regulation have largely focused on Thr 286 autophosphorylation after Ca 2ϩ /CaM binding. Indeed, G6P treatment of egg extract impairs PP1-mediated dephosphorylation of Thr 286 (25). However, this is unlikely to drive have not yet investigated these sites, they may contribute to full CaMKII activation.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Control of Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII)-mediated Caspase-2 Suppression by the B55β/Protein Phosphatase 2A (PP2A)

Huang¹,

Yang²,

Wojton³

et al. 2014

Journal of Biological Chemistry

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Background: CaMKII autophosphorylates at Thr 286 in cell-free lysates supplemented with glucose-6-phosphate (G6P). Results: The B55␤ and C subunits of PP2A interact with and dephosphorylate CaMKII at novel sites following addition of G6P. Conclusion: B55␤/PP2A is critical for stimulating CaMKII in the presence of G6P. Significance: This work identifies a novel role for a specific phosphatase complex in controlling CaMKII.

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Using Xenopus to understand human disease and developmental disorders

Sater

Moody

2017

Genesis

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Model animals are crucial to biomedical research. Among the commonly used model animals, the amphibian, Xenopus, has had tremendous impact because of its unique experimental advantages, cost effectiveness, and close evolutionary relationship with mammals as a tetrapod. Over the past 50 years, the use of Xenopus has made possible many fundamental contributions to biomedicine, and it is a cornerstone of research in cell biology, developmental biology, evolutionary biology, immunology, molecular biology, neurobiology, and physiology. The prospects for Xenopus as an experimental system are excellent: Xenopus is uniquely well-suited for many contemporary approaches used to study fundamental biological and disease mechanisms. Moreover, recent advances in high throughput DNA sequencing, genome editing, proteomics, and pharmacological screening are easily applicable in Xenopus, enabling rapid functional genomics and human disease modeling at a systems level.

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Metabolic Regulation of CaMKII Protein and Caspases in Xenopus laevis Egg Extracts

Cited by 9 publications

References 34 publications

Metabolic Activation of CaMKII by Coenzyme A

Metabolic Activation of CaMKII by Coenzyme A

Metabolic Control of Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII)-mediated Caspase-2 Suppression by the B55β/Protein Phosphatase 2A (PP2A)

Using Xenopus to understand human disease and developmental disorders

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