TNNI1, TNNI2 and TNNI3: Evolution, regulation, and protein structure–function relationships

Sheng, Juan Juan; Jin, Jian‐Ping

doi:10.1016/j.gene.2015.10.052

Cited by 92 publications

(101 citation statements)

References 141 publications

(162 reference statements)

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“…Given the delicate balance between members of the multicomponent regulatory system, specific isoforms of thin filament regulatory proteins likely evolved to match myosin isoform kinetics while keeping Ca 2+ -sensitivity within its physiological range. Indeed, muscle- and development-specific isoforms of troponin, tropomyosin and myosin have been identified [85–89], consistent with the notion that troponin-tropomyosin interaction equilibria are paired with myosin kinetics. Interestingly, isoform specificity is typically associated with the entire tropomyosin-troponin complex rather than with a single subunit (e.g., TnC, TnI or TnT) and correlates with specific myosin isoforms.…”

Section: Tropomyosin Governs Thin Filament Regulationsupporting

confidence: 54%

Structural determinants of muscle thin filament cooperativity

Moore

Campbell

Lehman

2016

Archives of Biochemistry and Biophysics

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End-to-end connections between adjacent tropomyosin molecules along the muscle thin filament allow long-range conformational rearrangement of the multicomponent filament structure. This process is influenced by Ca2+ and the troponin regulatory complexes, as well as by myosin crossbridge heads that bind to and activate the filament. Access of myosin crossbridges onto actin is gated by tropomyosin, and in the case of striated muscle filaments, troponin acts as a gatekeeper. The resulting tropomyosin-troponinmyosin on-off switching mechanism that controls muscle contractility is a complex cooperative and dynamic system with highly nonlinear behavior. Here, we review key information that leads us to view tropomyosin as central to the communication pathway that coordinates the multifaceted effectors that modulate and tune striated muscle contraction. We posit that an understanding of this communication pathway provides a framework for more in-depth mechanistic characterization of myopathy-associated mutational perturbations currently under investigation by many research groups.

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Section: Tropomyosin Governs Thin Filament Regulationsupporting

confidence: 54%

Structural determinants of muscle thin filament cooperativity

Moore

Campbell

Lehman

2016

Archives of Biochemistry and Biophysics

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“…Certain regions of cTnI seem to be more important functionally than other regions (Mogensen et al, 2015; Wei and Jin, 2015; Meyer and Chase, 2016; Sheng and Jin, 2016). It may be that any or most amino acid changes at certain TnI residues that occur in regions functionally important for regulating Ca 2+ -sensitivity would all be associated with increased Ca 2+ -sensitivity of force development.…”

Section: Discussionmentioning

confidence: 99%

Amino Acid Changes at Arginine 204 of Troponin I Result in Increased Calcium Sensitivity of Force Development

et al. 2016

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Mutations in human cardiac troponin I (cTnI) have been associated with restrictive, dilated, and hypertrophic cardiomyopathies. The most commonly occurring residue on cTnI associated with familial hypertrophic cardiomyopathy (FHC) is arginine (R), which is also the most common residue at which multiple mutations occur. Two FHC mutations are known to occur at cTnI arginine 204, R204C and R204H, and both are associated with poor clinical prognosis. The R204H mutation has also been associated with restrictive cardiomyopathy (RCM). To characterize the effects of different mutations at the same residue (R204) on the physiological function of cTnI, six mutations at R204 (C, G, H, P, Q, W) were investigated in skinned fiber studies. Skinned fiber studies showed that all tested mutations at R204 caused significant increases in Ca2+ sensitivity of force development (ΔpCa50 = 0.22–0.35) when compared to wild-type (WT) cTnI. Investigation of the interactions between the cTnI mutants and WT cardiac troponin C (cTnC) or WT cardiac troponin T (cTnT) showed that all the mutations investigated, except R204G, affected either or both cTnI:cTnT and cTnI:cTnC interactions. The R204H mutation affected both cTnI:cTnT and cTnI:cTnC interactions while the R204C mutation affected only the cTnI:cTnC interaction. These results suggest that different mutations at the same site on cTnI could have varying effects on thin filament interactions. A mutation in fast skeletal TnI (R174Q, homologous to cTnI R204Q) also significantly increased Ca2+ sensitivity of force development (ΔpCa50 = 0.16). Our studies indicate that known cTnI mutations associated with poor prognosis (R204C and R204H) exhibit large increases in Ca2+ sensitivity of force development. Therefore, other R204 mutations that cause similar increases in Ca2+ sensitivity are also likely to have poor prognoses.

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“…The complex has three regulatory proteins: troponin C, troponin C, and troponin T. Troponin C (TnC) binds to a calcium molecule [7]. Troponin I (TnI) is the inhibitory subunit while troponin T (TnT) binds to Tm [8,9].…”

Section: Introductionmentioning

confidence: 99%

Effect of starvation on expression of troponin complex genes and ER stress associated genes in skeletal muscles

Kwon¹,

Yoo²,

Ko³

et al. 2018

biomedicalresearch

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Little is known about the mechanism of gene expression changes in skeletal muscle during starvation. This study investigated the influence of starvation on gene expression of troponin complex (TnC, TnI and TnT), tropomyosin (Tpm), and endoplasmic reticulum (ER) stress associated proteins (BiP, calreticulin, PDI, and ATF6) in three kinds of skeletal muscles of Gryllus bimaculatus. Dorsal ventral flight muscle (DVM), dorsal longitudinal, and dorsal wing flight muscles (DWM) were identified as typical skeletal muscles by H&E staining. Obvious gene expression was detected in the DVM, but not in the DLM or DWM. In addition to gene expression in DVM, gene expression of decorin, a type of myokine, was also significantly increased by starvation. This is the first study that reports the effect of starvation on expression of troponin complex genes and ER stress associated genes in three types of skeletal muscles.

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TNNI1, TNNI2 and TNNI3: Evolution, regulation, and protein structure–function relationships

Cited by 92 publications

References 141 publications

Structural determinants of muscle thin filament cooperativity

Structural determinants of muscle thin filament cooperativity

Amino Acid Changes at Arginine 204 of Troponin I Result in Increased Calcium Sensitivity of Force Development

Effect of starvation on expression of troponin complex genes and ER stress associated genes in skeletal muscles

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