Coupling of cell energetics with membrane metabolic sensing. Integrative signaling through creatine kinase phosphotransfer disrupted by M-CK gene knock-out

M Roselle Abraham; Vitaliy A Selivanov; Denice M Hodgson; Darko Pucar; Leonid V Zingman; Be Wieringa; Petras P Dzeja; Alexey E Alekseev; Andre Terzic

doi:10.1074/jbc.M201777200

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Coupling of cell energetics with membrane metabolic sensing. Integrative signaling through creatine kinase phosphotransfer disrupted by M-CK gene knock-out

Journal article

Open access

Peer reviewed

Coupling of cell energetics with membrane metabolic sensing. Integrative signaling through creatine kinase phosphotransfer disrupted by M-CK gene knock-out

M Roselle Abraham, Vitaliy A Selivanov, Denice M Hodgson, Darko Pucar, Leonid V Zingman, Be Wieringa, Petras P Dzeja, Alexey E Alekseev and Andre Terzic

The Journal of biological chemistry, Vol.277(27), pp.24427-24434

07/05/2002

DOI: 10.1074/jbc.M201777200

PMID: 11967264

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Abstract

Transduction of metabolic signals is essential in preserving cellular homeostasis. Yet, principles governing integration and synchronization of membrane metabolic sensors with cell metabolism remain elusive. Here, analysis of cellular nucleotide fluxes and nucleotide-dependent gating of the ATP-sensitive K+ (K(ATP)) channel, a prototypic metabolic sensor, revealed a diffusional barrier within the submembrane space, preventing direct reception of cytosolic signals. Creatine kinase phosphotransfer, captured by 18O-assisted 31P NMR, coordinated tightly with ATP turnover, reflecting the cellular energetic status. The dynamics of high energy phosphoryl transfer through the creatine kinase relay permitted a high fidelity transmission of energetic signals into the submembrane compartment synchronizing K(ATP) channel activity with cell metabolism. Knock-out of the creatine kinase M-CK gene disrupted signal delivery to K(ATP) channels and generated a cellular phenotype with increased electrical vulnerability. Thus, in the compartmentalized cell environment, phosphotransfer systems shunt diffusional barriers and secure regimented signal transduction integrating metabolic sensors with the cellular energetic network.

Creatine Kinase - deficiency

Magnetic Resonance Spectroscopy

Creatine Kinase, MM Form

Isoenzymes - genetics

Heart - physiology

Potassium Channels - physiology

Isoenzymes - deficiency

Mice, Knockout

Creatine Kinase - genetics

Animals

Membrane Potentials

Isoenzymes - metabolism

Models, Biological

Adenosine Triphosphate - metabolism

Myocardium - metabolism

Creatine Kinase - metabolism

Cell Membrane - metabolism

Mice

Adenosine Diphosphate - metabolism

Kinetics

Energy Metabolism - physiology

Details

Title: Subtitle: Coupling of cell energetics with membrane metabolic sensing. Integrative signaling through creatine kinase phosphotransfer disrupted by M-CK gene knock-out
Creators: M Roselle Abraham - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology, and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA
Vitaliy A Selivanov
Denice M Hodgson
Darko Pucar
Leonid V Zingman
Be Wieringa
Petras P Dzeja
Alexey E Alekseev
Andre Terzic
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(27), pp.24427-24434
DOI: 10.1074/jbc.M201777200
PMID: 11967264
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Grant note: HL-64822 / NHLBI NIH HHS HL-07111 / NHLBI NIH HHS
Language: English
Date published: 07/05/2002
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984094481102771

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