Physiological Functions of the Giant Elastic Protein Titin in Mammalian Striated Muscle

Fukuda, Norio; Granzier, Henk; Ishiwata, Shin’ichi; Kurihara, Satoshi

doi:10.2170/physiolsci.rv005408

Cited by 90 publications

(62 citation statements)

References 99 publications

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“…This is in agreement with different calcium kinetics (Baylor and Hollingworth, 2003) and different PEVK segment length (Neagoe et al, 2003;Prado et al, 2005;Fukuda et al, 2008).…”

Section: Static Stiffness Dependence On Sarcomere Lengthsupporting

confidence: 84%

“…Static stiffness was detected and characterized for the first time in single intact skeletal muscle fibres isolated from FDB mouse muscle (Colombini et al, 2009). Subsequently, the analysis was extended to fast and slow mouse muscles such as EDL and soleus (Nocella et al, 2012) that express a short and a long titin isoform, respectively, with different mechanical properties (Prado et al, 2005;Fukuda et al, 2008).…”

Section: Static Stiffness In Mouse Muscle Fibresmentioning

confidence: 99%

“…To better investigate the role of titin, we measured static stiffness in soleus and in EDL (Nocella et al, 2012), which express the N2A titin isoform with long and short PEVK segments and lower and higher proportions of E-rich motifs, respectively (Neagoe et al, 2003;Prado et al, 2005;Fukuda et al, 2008). It is well known that the I-band portion of titin, especially the PEVK segment, has elastic properties that act as a molecular spring whose bending stiffness increases upon Ca 2+ binding to E-rich motifs in the PEVK segment (Labeit et al, 2003).…”

Section: Static Stiffness Dependence On Sarcomere Lengthmentioning

confidence: 99%

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Non-crossbridge stiffness in active muscle fibres

Colombini

Nocella

Bagni

2016

Journal of Experimental Biology

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Stretching of an activated skeletal muscle induces a transient tension increase followed by a period during which the tension remains elevated well above the isometric level at an almost constant value. This excess of tension in response to stretching has been called 'static tension' and attributed to an increase in fibre stiffness above the resting value, named 'static stiffness'. This observation was originally made, by our group, in frog intact muscle fibres and has been confirmed more recently, by us, in mammalian intact fibres. Following stimulation, fibre stiffness starts to increase during the latent period well before crossbridge force generation and it is present throughout the whole contraction in both single twitches and tetani. Static stiffness is dependent on sarcomere length in a different way from crossbridge force and is independent of stretching amplitude and velocity. Static stiffness follows a time course which is distinct from that of active force and very similar to the myoplasmic calcium concentration time course. We therefore hypothesize that static stiffness is due to a calcium-dependent stiffening of a noncrossbridge sarcomere structure, such as the titin filament. According to this hypothesis, titin, in addition to its well-recognized role in determining the muscle passive tension, could have a role during muscle activity.

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“…This is in agreement with different calcium kinetics (Baylor and Hollingworth, 2003) and different PEVK segment length (Neagoe et al, 2003;Prado et al, 2005;Fukuda et al, 2008).…”

Section: Static Stiffness Dependence On Sarcomere Lengthsupporting

confidence: 84%

Section: Static Stiffness In Mouse Muscle Fibresmentioning

confidence: 99%

Section: Static Stiffness Dependence On Sarcomere Lengthmentioning

confidence: 99%

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Non-crossbridge stiffness in active muscle fibres

Colombini

Nocella

Bagni

2016

Journal of Experimental Biology

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“…In diastole, force-generating reactions of cross-bridges with actin are inhibited, ATP hydrolysis is relatively low, and the sarcomere is relatively extensible (2). Properties of the giant protein titin dominate the compliance of the relaxed sarcomere (3). Interactions of thin filament regulatory proteins, the troponin heterotrimeric complex, and Tm hinder the actin-cross-bridge reaction and establish the B-state.…”

mentioning

confidence: 99%

Protein Phosphorylation and Signal Transduction in Cardiac Thin Filaments

Solaro

Kobayashi

2011

Journal of Biological Chemistry

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Homeostasis of cardiac function requires significant adjustments in sarcomeric protein phosphorylation. The existence of unique peptides in cardiac sarcomeres, which are substrates for a multitude of kinases, strongly supports this concept (1). We focus here on the troponin complex of the thin filaments, which contain two major proteins that participate in these phosphoryl group transfer reactions: the inhibitory protein (cardiac troponin (cTn) 2 I) and the tropomyosin (Tm)-binding protein (cTnT). We describe the relatively new understanding of the molecular mechanisms of thin filament-based control of the heartbeat and how these mechanisms are altered by phosphorylation. We discuss new concepts regarding the relation between the beat of the heart and the location of thin filament proteins and their long-and short-range interactions. We also discuss elucidation of mechanisms by which these phosphorylations exacerbate or ameliorate effects of mutations in the myofilament proteins that are linked to familial cardiomyopathies. Fig. 1 depicts an A-band region of the cardiac thin filament functional unit in the diastolic and systolic states. In diastole, force-generating reactions of cross-bridges with actin are inhibited, ATP hydrolysis is relatively low, and the sarcomere is relatively extensible (2). Properties of the giant protein titin dominate the compliance of the relaxed sarcomere (3). Interactions of thin filament regulatory proteins, the troponin heterotrimeric complex, and Tm hinder the actin-cross-bridge reaction and establish the B-state. Calcium binding to a single regulatory site on cTnC triggers a release from this inhibited state by modifications of interactions among actin, Tm, and Tn. Thin Filaments during the Relaxed StateEvidence derived from the core crystal structure of cardiac Tn (4), from elucidation of the structures by NMR (5), from biochemical investigations of protein-protein interactions (6, 7), and from reconstructions and single-particle analysis of electron micrographs of reconstituted myofilament preparations (8, 9) provided the basis for the illustration in Fig. 1 (see Ref. 6 for a review). Apart from the lack of a thin filament lattice in the Tn core crystal structure, there was no structural information on significant regions, including the tail region of cTnT, an inhibitory peptide (Ip; which tethers cTnI to actin), the unique N-terminal peptide (ϳ30 amino acids), and portions of the far C-terminal domain of cTnI. Thus, Fig. 1 (upper) shows binding of cTnI to actin via two regions, the highly basic Ip and a second actin-binding region. Importantly, these regions flank a switch peptide, which binds to cTnC when Ca 2ϩ binds to the N-terminal lobe of cTnC, which houses the regulatory Ca 2ϩ -binding site, thereby participating in the mechanism by which Tn releases the thin filament from inhibition.The C-terminal mobile domain of cTnI beyond the second actin-binding site may also participate in establishing the relaxed state. Two observations point to this possibility. The first is a ...

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“…Such filaments would be responsible for producing the voltage required to maintain the centering, the length and the ideal overlap between the actin and myosin. Also, it keeps the active sites of actin in suitable for the coupling heads of MCP angular position, and ensure the maintenance of muscle passive tension due to its mechanical properties (94,95,96). Labeit et al (64) propose that the maintenance of muscle passive tension was still associated with the Ca 2+ dependent mechanism, due to a high affinity and coupling capacity between Ca 2+ and the active site of titin filaments.…”

Section: Elastic Components In Parallel Recruitment Theorymentioning

confidence: 99%

Variation in isometric force after active shortening and lengthening and their mechanisms: a review

Lima

Farinatti²,

Monteiro

et al. 2014

Fisioter. mov.

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Introduction:The isometric force history dependence of skeletal muscle has been studied along the last one hundred years. Several theories have been formulated to explain and establish the causes of the phenomenon, but not successfully, as they have not been fully accepted and demonstrated, and much controversy on such a subject still remains. Objective: To present a systematic literature review on the dynamics of the mechanisms of force depression and force enhancement after active shortening and lengthening, respectively, identifying the key variables involved in the phenomenon, and to date to present the main theories and hypothesis developed trying to explaining it. Method: The procedure of literature searching complied the major databases, including articles either, those which directly investigated the phenomena of force depression and force enhancement or those which presented possible causes and mechanisms associated with their respective events, from the earliest studies published until the year of 2010. Results: 97

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Physiological Functions of the Giant Elastic Protein Titin in Mammalian Striated Muscle

Cited by 90 publications

References 99 publications

Non-crossbridge stiffness in active muscle fibres

Non-crossbridge stiffness in active muscle fibres

Protein Phosphorylation and Signal Transduction in Cardiac Thin Filaments

Variation in isometric force after active shortening and lengthening and their mechanisms: a review

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