Function of Creatine Kinase Localization in Muscle Contraction

Koons, Stephen J.; Cooke, Roger

doi:10.1007/978-1-4684-5107-8_10

Cited by 7 publications

(6 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, AMPK activity is subject to localized regulation by AMP pools. In addition, LKB1 target activation depends on its subcellular localization and transcriptional expression (4,(18)(19)(20)40). Therefore, we hypothesized that the amount of the LKB1 complex relative to activated AMPK will uniquely impact myofilament function.…”

Section: Discussionmentioning

confidence: 99%

“…We propose that a potential mechanism by which AMPK protects the heart during cardiac disease is by acting as a nodal point for sensing changes in cellular energetics and then appropriately targeting the contractile apparatus to alter contractility. However, exploring the mechanism of AMPK-based protection against heart failure is complicated by two critical findings: 1) CK and AK enzymes are localized to the myofilaments (4,18), and 2) stoichiometry of the upstream activator LKB1/Mo25/ STRAD complex (LKB1 complex) and AMPK drives AMPK-target activity (19,20). This suggests that both localized adenine nucleotides pools and the stoichiometric activator complex are indispensable for driving AMPKdependent targeting of myofilament proteins.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

LKB1/Mo25/STRAD Uniquely Impacts Sarcomeric Contractile Function and Posttranslational Modification

Behunin

Lopez-Pier

Birch

et al. 2015

Biophysical Journal

View full text Add to dashboard Cite

The myocardium undergoes extensive metabolic and energetic remodeling during the progression of cardiac disease. Central to remodeling are changes in the adenine nucleotide pool. Fluctuations in these pools can activate AMP-activated protein kinase (AMPK), the central regulator of cellular energetics. Binding of AMP to AMPK not only allosterically activates AMPK but also promotes phosphorylation of AMPK by an upstream kinase complex, LKB1/Mo25/STRAD (liver kinase B 1, mouse protein 25, STE-related adaptor protein). AMPK phosphorylation by the LKB1 complex results in a substantial increase in AMPK activity. Molecular targeting by the LKB1 complex depends on subcellular localization and transcriptional expression. Yet, little is known about the ability of the LKB1 complex to modulate targeting of AMPK after activation. Accordingly, we hypothesized that differing stoichiometric ratios of LKB1 activator complex to AMPK would uniquely impact myofilament function. Demembranated rat cardiac trabeculae were incubated with varying ratios of the LKB1 complex to AMPK or the LKB1 complex alone. After incubation, we measured the Ca(2+) sensitivity of tension, rate constant for tension redevelopment, maximum tension generation, length-dependent activation, cooperativity, and sarcomeric protein phosphorylation status. We found that the Ca(2+) sensitivity of tension and cross-bridge dynamics were dependent on the LKB1 complex/AMPK ratio. We also found that the LKB1 complex desensitizes and suppresses myofilament function independently of AMPK. A phospho-proteomic analysis of myofilament proteins revealed site-specific changes in cardiac Troponin I (cTnI) phosphorylation, as well as a unique distribution of cTnI phosphospecies that were dependent on the LKB1 complex/ AMPK ratio. Fibers treated with the LKB1 complex alone did not alter cTnI phosphorylation or phosphospecies distribution. However, LKB1 complex treatment independent of AMPK increased phosphorylation of myosin-binding protein C. Therefore, we conclude that the LKB1/AMPK signaling axis is able to alter muscle function through multiple mechanisms.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LKB1/Mo25/STRAD Uniquely Impacts Sarcomeric Contractile Function and Posttranslational Modification

Behunin

Lopez-Pier

Birch

et al. 2015

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…Given the physical barriers to rapid diffusion within the myocyte, physical association of CK, AK, and other key enzymes in the phosphotransferase system optimizes efficient transfer of phosphoryl groups to adenosine diphosphate (ADP) [13]. These phosphotransfer components exist in discrete microdomains and are localized to sarcomeric myofibrils acting as hubs for energy “sensing” [14, 15]. More importantly, these phosphotransferase enzymes display remarkable plasticity in function and compartmentation during energy stress [16].…”

Section: Introductionmentioning

confidence: 99%

Liver Kinase B1 complex acts as a novel modifier of myofilament function and localizes to the Z-disk in cardiac myocytes

Behunin

Lopez-Pier

Mayfield

et al. 2016

Archives of Biochemistry and Biophysics

View full text Add to dashboard Cite

Contractile perturbations downstream of Ca2+ binding to troponin C, the so-called sarcomere-controlled mechanisms, represent the earliest indicators of energy remodeling in the diseased heart [1]. Central to cellular energy “sensing” is the adenosine monophosphate-activated kinase (AMPK) pathway, which is known to directly target myofilament proteins and alter contractility [2-6]. We previously showed that the upstream AMPK kinase, LKB1/MO25/STRAD, impacts myofilament function independently of AMPK [5]. Therefore, we hypothesized that the LKB1 complex associated with myofilament proteins and that alterations in energy signaling modulated targeting or localization of the LKB1 complex to the myofilament. Using an integrated strategy of myofilament mechanics, immunoblot analysis, co-immunoprecipitation, mass spectroscopy, and immunofluorescence, we showed that 1) LKB1 and MO25 associated with myofibrillar proteins, 2) cellular energy stress re-distributed AMPK/LKB1 complex proteins within the sarcomere, and 3) the LKB1 complex localized to the Z-Disk and interacted with cytoskeletal and energy-regulating proteins, including vinculin and ATP Synthase (Complex V). These data represent a novel role for LKB1 complex proteins in myofilament function and myocellular “energy” sensing in the heart.

show abstract

“…In this function, creatine kinase transfers a phosphate from ATP to creatinc forming creatine phosphate. The creatine phosphate is *'shuttled" o u t of the mitochondrion into the cytosol and is then available as a substrate for cytosolic creatinc kinase [ Koons and Cooke, 1986;Bessman, 19851.…”

Section: Introductionmentioning

confidence: 99%

Comparative biochemical characteristics of the cat and rabbit urinary bladder

et al. 1994

View full text Add to dashboard Cite

The cat and the rabbit are two of the most popular models for the study of lower urinary bladder function. The cat has been used extensively for in vivo studies of spinal and supra‐spinal micturition reflexes. In contrast, the rabbit has been used extensively for the in vitro study of bladder function. Although the cat and rabbit bladders are approximately the same mass, the cat bladder can generate approximately 6 times the intravesical pressure than the rabbit bladder at the same volume (in vitro response to field stimulation). In order to determine it the increased pressure generation is related to increased cellular energetics, we compared the intracellular concentrations of ATP and creatine phosphate (CP), and the enzyme activities of three enzymes which have important functions in cellular energetics: creatine kinase, citrate synthase, and malic dehydrogenase between the cat and rabbit urinary bladder. The results can be summarized as follows: (I) The bladder weight of the cat and rabbit are similar. (2) The isolated cat bladder can generate approximately 6 times the intravesical pressure of the isolated rabbit bladder, (3) The ATP and CP concentrations of the rabbit are significantly greater than the concentrations in the cat bladder, (4) The hydroxyproline concentration is significantly greater in the eat than the rabbit, (5) The maximum activities of creatine kinase, citrate synthase, and malic dehydrogenase are significantly lower in the cat than the rabbit. In general, it is clear that the ability of the cat to generate high intravesical pressures is not correlated with increased tissue high energy phosphate concentrations, or high enzymatic activities of three specific cytosolic or mitochondrial enzymes. © 1994 Wiley‐Liss, Inc.

show abstract

Function of Creatine Kinase Localization in Muscle Contraction

Cited by 7 publications

References 15 publications

LKB1/Mo25/STRAD Uniquely Impacts Sarcomeric Contractile Function and Posttranslational Modification

LKB1/Mo25/STRAD Uniquely Impacts Sarcomeric Contractile Function and Posttranslational Modification

Liver Kinase B1 complex acts as a novel modifier of myofilament function and localizes to the Z-disk in cardiac myocytes

Comparative biochemical characteristics of the cat and rabbit urinary bladder

Contact Info

Product

Resources

About