scholarly journals 14–3-3 protein regulation of excitation–contraction coupling

2021 ◽  
Author(s):  
Walter C. Thompson ◽  
Paul H. Goldspink
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Force Generation ◽  
Client Protein ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Cellular Processes ◽  
Disease States ◽  
Growing Body ◽  
Client Proteins

Abstract 14–3-3 proteins (14–3-3 s) are a family of highly conserved proteins that regulate many cellular processes in eukaryotes by interacting with a diverse array of client proteins. The 14–3-3 proteins have been implicated in several disease states and previous reviews have condensed the literature with respect to their structure, function, and the regulation of different cellular processes. This review focuses on the growing body of literature exploring the important role 14–3-3 proteins appear to play in regulating the biochemical and biophysical events associated with excitation–contraction coupling (ECC) in muscle. It presents both a timely and unique analysis that seeks to unite studies emphasizing the identification and diversity of 14–3-3 protein function and client protein interactions, as modulators of muscle contraction. It also highlights ideas within these two well-established but intersecting fields that support further investigation with respect to the mechanistic actions of 14–3-3 proteins in the modulation of force generation in muscle.

scholarly journals Muscle glycogen and metabolic regulation

2004 ◽  
Vol 63 (2) ◽  
pp. 217-220 ◽  
Author(s):  
Mark Hargreaves
Keyword(s):  
Muscle Glycogen ◽  
Insulin Action ◽  
Metabolic Regulation ◽  
Strenuous Exercise ◽  
Glycogen Depletion ◽  
Excitation Contraction Coupling ◽  
Glycogen Resynthesis ◽  
Contraction Coupling ◽  
Cellular Processes ◽  
Exercise Induced

Muscle glycogen is an important fuel for contracting skeletal muscle during prolonged strenuous exercise, and glycogen depletion has been implicated in muscle fatigue. It is also apparent that glycogen availability can exert important effects on a range of metabolic and cellular processes. These processes include carbohydrate, fat and protein metabolism during exercise, post-exercise glycogen resynthesis, excitation–contraction coupling, insulin action and gene transcription. For example, low muscle glycogen is associated with reduced muscle glycogenolysis, increased glucose and NEFA uptake and protein degradation, accelerated glycogen resynthesis, impaired excitation–contraction coupling, enhanced insulin action and potentiation of the exercise-induced increases in transcription of metabolic genes. Future studies should identify the mechanisms underlying, and the functional importance of, the association between glycogen availability and these processes.

Peroxynitrite induces contractile dysfunction and lipid peroxidation in the diaphragm

1999 ◽  
Vol 87 (2) ◽  
pp. 783-791 ◽  
Author(s):  
G. Supinski ◽  
D. Stofan ◽  
L. A. Callahan ◽  
D. Nethery ◽  
T. M. Nosek ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Protein Function ◽  
Muscle Force ◽  
Force Generation ◽  
Diaphragm Muscle ◽  
Fiber Bundles ◽  
Muscle Dysfunction ◽  
Contractile Dysfunction ◽  
Disease States ◽  
Generating Capacity

Peroxynitrite may be generated in and around muscles in several pathophysiological conditions (e.g., sepsis) and may induce muscle dysfunction in these disease states. The effect of peroxynitrite on muscle force generation has not been directly assessed. The purpose of the present study was to assess the effects of peroxynitrite administration on diaphragmatic force-generating capacity in 1) intact diaphragm muscle fiber bundles (to model the effects produced by exposure of muscles to extracellular peroxynitrite) and 2) single skinned diaphragm muscle fibers (to model the effects of intracellular peroxynitrite on contractile protein function) by examining the effects of both peroxynitrite and a peroxynitrite-generating solution, 3-morpholinosydnonimine, on force vs. pCa characteristics. In intact diaphragm preparations, peroxynitrite reduced diaphragm force generation and increased muscle levels of 4-hydroxynonenal (an index of lipid peroxidation). In skinned fibers, both peroxynitrite and 3-morpholinosydnonimine reduced maximum calcium-activated force. These data indicate that peroxynitrite is capable of producing significant diaphragmatic contractile dysfunction. We speculate that peroxynitrite-mediated alterations may be responsible for much of the muscle dysfunction seen in pathophysiological conditions such as sepsis.

Temporal aspects of excitation-contraction coupling in airway smooth muscle

2001 ◽  
Vol 91 (5) ◽  
pp. 2266-2274 ◽  
Author(s):  
Gary C. Sieck ◽  
Young-Soo Han ◽  
Christina M. Pabelick ◽  
Y. S. Prakash
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Force Generation ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Caged Atp ◽  
Cross Bridge

In airway smooth muscle (ASM), ACh induces propagating intracellular Ca2+ concentration ([Ca2+]i) oscillations (5–30 Hz). We hypothesized that, in ASM, coupling of elevations and reductions in [Ca2+]i to force generation and relaxation (excitation-contraction coupling) is slower than ACh-induced [Ca2+]i oscillations, leading to stable force generation. When we used real-time confocal imaging, the delay between elevated [Ca2+]i and contraction in intact porcine ASM cells was found to be ∼450 ms. In β-escin-permeabilized ASM strips, photolytic release of caged Ca2+ resulted in force generation after ∼800 ms. When calmodulin (CaM) was added, this delay was shortened to ∼500 ms. In the presence of exogenous CaM and 100 μM Ca2+, photolytic release of caged ATP led to force generation after ∼80 ms. These results indicated significant delays due to CaM mobilization and Ca2+-CaM activation of myosin light chain kinase but much shorter delays introduced by myosin light chain kinase-induced phosphorylation of the regulatory myosin light chain MLC20 and cross-bridge recruitment. This was confirmed by prior thiophosphorylation of MLC20, in which force generation occurred ∼50 ms after photolytic release of caged ATP, approximating the delay introduced by cross-bridge recruitment alone. The time required to reach maximum steady-state force was >15 s. Rapid chelation of [Ca2+]i after photolytic release of caged diazo-2 resulted in relaxation after a delay of ∼1.2 s and 50% reduction in force after ∼57 s. We conclude that in ASM cells agonist-induced [Ca2+]i oscillations are temporally and spatially integrated during excitation-contraction coupling, resulting in stable force production.

scholarly journals In Vivo Methods to Study Protein-Protein Interactions as Key Players in Mycobacterium tuberculosis Virulence

2019 ◽  
Author(s):  
Romain Veyron-Churlet ◽  
Camille Locht
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Protein Interactions ◽  
Protein Function ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Unknown Protein ◽  
Transient Interactions ◽  
Protein Complementation

Studies on Protein-Protein interactions (PPI) can be helpful for the annotation of unknown protein function and for the understanding of cellular processes, such as specific virulence mechanisms developed by bacterial pathogens. In that context, several methods have been extensively used in recent years for the characterization of Mycobacterium tuberculosis PPI to further decipher TB pathogenesis. This review aims at compiling the most striking results based on in vivo methods (yeast and bacterial two-hybrid systems, protein complementation assays) for the specific study of PPI in mycobacteria. Moreover, newly developed methods, such as in-cell native mass resonance and proximity-dependent biotinylation identification, will have a deep impact on future mycobacterial research, as they are able to perform dynamic (transient interactions) and integrative (multiprotein complexes) analyses.

scholarly journals Client proximity enhancement inside cellular membrane-less compartments governed by client-compartment interactions

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Daesun Song ◽  
Yongsang Jo ◽  
Jeong-Mo Choi ◽  
Yongwon Jung
Keyword(s):  
Phase Separation ◽  
Protein Interactions ◽  
Cellular Membrane ◽  
Formation Mechanisms ◽  
Cellular Processes ◽  
Quantitative Measurements ◽  
Wide Range ◽  
Client Proteins ◽  
Spatiotemporal Control

Abstract Membrane-less organelles or compartments are considered to be dynamic reaction centers for spatiotemporal control of diverse cellular processes in eukaryotic cells. Although their formation mechanisms have been steadily elucidated via the classical concept of liquid–liquid phase separation, biomolecular behaviors such as protein interactions inside these liquid compartments have been largely unexplored. Here we report quantitative measurements of changes in protein interactions for the proteins recruited into membrane-less compartments (termed client proteins) in living cells. Under a wide range of phase separation conditions, protein interaction signals were vastly increased only inside compartments, indicating greatly enhanced proximity between recruited client proteins. By employing an in vitro phase separation model, we discovered that the operational proximity of clients (measured from client–client interactions) could be over 16 times higher than the expected proximity from actual client concentrations inside compartments. We propose that two aspects should be considered when explaining client proximity enhancement by phase separation compartmentalization: (1) clients are selectively recruited into compartments, leading to concentration enrichment, and more importantly, (2) recruited clients are further localized around compartment-forming scaffold protein networks, which results in even higher client proximity.

scholarly journals Late Embryogenesis Abundant Protein–Client Protein Interactions

Plants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 814
Author(s):  
Lynnette M. A. Dirk ◽  
Caser Ghaafar Abdel ◽  
Imran Ahmad ◽  
Izabel Costa Silva Neta ◽  
Cristiane Carvalho Pereira ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Late Embryogenesis Abundant ◽  
Disordered Proteins ◽  
Late Embryogenesis Abundant Protein ◽  
Client Protein ◽  
Protective Function ◽  
Abundant Protein ◽  
Intrinsically Disordered ◽  
Late Embryogenesis ◽  
Client Proteins

The intrinsically disordered proteins belonging to the LATE EMBRYOGENESIS ABUNDANT protein (LEAP) family have been ascribed a protective function over an array of intracellular components. We focus on how LEAPs may protect a stress-susceptible proteome. These examples include instances of LEAPs providing a shield molecule function, possibly by instigating liquid-liquid phase separations. Some LEAPs bind directly to their client proteins, exerting a holdase-type chaperonin function. Finally, instances of LEAP–client protein interactions have been documented, where the LEAP modulates (interferes with) the function of the client protein, acting as a surreptitious rheostat of cellular homeostasis. From the examples identified to date, it is apparent that client protein modulation also serves to mitigate stress. While some LEAPs can physically bind and protect client proteins, some apparently bind to assist the degradation of the client proteins with which they associate. Documented instances of LEAP–client protein binding, even in the absence of stress, brings to the fore the necessity of identifying how the LEAPs are degraded post-stress to render them innocuous, a first step in understanding how the cell regulates their abundance.

scholarly journals Mechanisms of the 14-3-3 Protein Function: Regulation of Protein Function Through Conformational Modulation

2014 ◽  
pp. S155-S164 ◽  
Author(s):  
V. OBSILOVA ◽  
M. KOPECKA ◽  
D. KOSEK ◽  
M. KACIROVA ◽  
S. KYLAROVA ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Specific Protein ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Protein Protein Interactions ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Binding Partners ◽  
Regulatory Functions

Many aspects of protein function regulation require specific protein-protein interactions to carry out the exact biochemical and cellular functions. The highly conserved members of the 14-3-3 protein family mediate such interactions and through binding to hundreds of other proteins provide multitude of regulatory functions, thus playing key roles in many cellular processes. The 14-3-3 protein binding can affect the function of the target protein in many ways including the modulation of its enzyme activity, its subcellular localization, its structure and stability, or its molecular interactions. In this minireview, we focus on mechanisms of the 14-3-3 protein-dependent regulation of three important 14-3-3 binding partners: yeast neutral trehalase Nth1, regulator of G-protein signaling 3 (RGS3), and phosducin.

Sign in / Sign up

Export Citation Format

Share Document