Adenylate kinase phosphotransfer communicates cellular energetic signals to ATP-sensitive potassium channels. Proc Natl Acad Sci U S A 2001 Jun 19;98(13):7623-8
Date
06/08/2001Pubmed ID
11390963Pubmed Central ID
PMC34718DOI
10.1073/pnas.121038198Scopus ID
2-s2.0-0035912761 (requires institutional sign-in at Scopus site) 226 CitationsAbstract
Transduction of energetic signals into membrane electrical events governs vital cellular functions, ranging from hormone secretion and cytoprotection to appetite control and hair growth. Central to the regulation of such diverse cellular processes are the metabolism sensing ATP-sensitive K+ (K(ATP)) channels. However, the mechanism that communicates metabolic signals and integrates cellular energetics with K(ATP) channel-dependent membrane excitability remains elusive. Here, we identify that the response of K(ATP) channels to metabolic challenge is regulated by adenylate kinase phosphotransfer. Adenylate kinase associates with the K(ATP) channel complex, anchoring cellular phosphotransfer networks and facilitating delivery of mitochondrial signals to the membrane environment. Deletion of the adenylate kinase gene compromised nucleotide exchange at the channel site and impeded communication between mitochondria and K(ATP) channels, rendering cellular metabolic sensing defective. Assigning a signal processing role to adenylate kinase identifies a phosphorelay mechanism essential for efficient coupling of cellular energetics with K(ATP) channels and associated functions.
Author List
Carrasco AJ, Dzeja PP, Alekseev AE, Pucar D, Zingman LV, Abraham MR, Hodgson D, Bienengraeber M, Puceat M, Janssen E, Wieringa B, Terzic AMESH terms used to index this publication - Major topics in bold
Adenosine DiphosphateAdenosine Monophosphate
Adenosine Triphosphate
Adenylate Kinase
Animals
COS Cells
Cell Membrane
Cells, Cultured
Dinitrophenols
Guinea Pigs
Heart
Isoenzymes
Kinetics
Mice
Mice, Knockout
Mitochondria
Models, Biological
Myocardium
Oligomycins
Potassium Channels
Potassium Channels, Inwardly Rectifying
Recombinant Proteins
Sarcolemma
Signal Transduction
Transfection
