Regulation of Muscle Contraction: Binding of Troponin and Its Components to Actin and Tropomyosin

Hitchcock, Sarah E.

doi:10.1111/j.1432-1033.1975.tb03993.x

Cited by 107 publications

(53 citation statements)

References 37 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The TnI⅐TnC complex has a very weak affinity for actin⅐Tm in the presence of calcium (41)(42)(43)(44). Therefore, our data indicate that the measured affinity is due to a secondary interaction specific to the presence of C-terminal TnT "head" region.…”

Section: Discussionmentioning

confidence: 99%

Tropomyosin Exon 6b Is Troponin-specific and Required for Correct Acto-myosin Regulation

Maytum

Bathe²,

Konrad

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

The specificity of tropomyosin (Tm) exon 6b for interaction with and functioning of troponin (Tn) has been studied using recombinant fibroblast Tm isoforms 5a and 5b. These isoforms differ internally by exons 6a/6b and possess non-muscle exons 1b/9d at the termini, hence they lack the primary TnT 1 -tropomyosin interaction, allowing study of exon 6 exchange in isolation from this. Using kinetic techniques to measure regulation of myosin S1 binding to actin and fluorescently labeled Tm to directly measure Tn binding, we show that binding of Tn to both isoforms is similar (0.1-0.5 M) and both produce well regulated systems. Calcium has little effect on Tn binding to the actin⅐Tm complex and both exons produce a 3-fold reduction in the S1 binding rate to actin⅐Tm⅐Tn in its absence. This confirms previous results that show exon 6 has little influence on Tn affinity to actin⅐Tm or its ability to fully inhibit the acto-myosin interaction. Thin filaments reconstituted with Tn and Tm5a or skeletal Tm (containing exon 6b) show nearly identical calcium dependence of acto-myosin regulation. However, Tm5b produces a dramatic increase in calcium sensitivity, shifting the activation mid-point by almost an order of magnitude. This shows that exon 6 sequence and, hence, Tm structure in this region have a significant effect upon the calcium regulation of Tn. This finding supports evidence that familial hypertrophic cardiomyopathy mutations occurring adjacent to this region can effect calcium regulation.

show abstract

Section: Discussionmentioning

confidence: 99%

Tropomyosin Exon 6b Is Troponin-specific and Required for Correct Acto-myosin Regulation

Maytum

Bathe²,

Konrad

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…22 Affinity chromatography was performed at 25 °C. Each of the isolated aorta calponins (3.3 mg) and gizzard calponins (4 mg) in 20 mM Tris HC1 buffer (pH 7.0) containing 2 mM MgCl 2 ,0.5 mM DTT, and either 2 mM CaCl 2 or 1 mM EGTA was applied to the affinity column ( 1 x 5 cm).…”

Section: Affinity Chromatographymentioning

confidence: 99%

Vascular smooth muscle calponin. A novel troponin T-like protein.

1988

View full text Add to dashboard Cite

SUMMARY In a search for additional Ca 2+ regulatory components in vascular smooth muscle, a novel troponin T-like protein was purified from bovine aorta smooth muscle. The isolated protein was separated into several isoforms on isoelectric focusing. The major isoelectric variants were focused in the pH region of 8.4 to 9.1. The protein had slightly different molecular masses in the M r range of 35,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its molar ratio relative to tropomyosin in the muscle extract was estimated to be 0.9 = 1.0. The novel protein bound to the immobilized calmodulin and exhibited a number of common physicochemical properties with gizzard (Af r = 34,000) calmodulin-binding and F-actin-binding protein. The aorta and gizzard proteins were immunologically cross-reactive. Both proteins shared a common antigenic determinant with COOHterminal segments of rabbit skeletal and bovine cardiac troponin T and bound to the immobilized smooth muscle tropomyosin. Both proteins interacted with rabbit skeletal troponin C in the presence and absence of Ca 2 + , but they did not interact with troponin I. These results suggest that the novel protein, which is designated calponin, may be a specialized component of smooth muscle thin filament involved in the regulation of contractile apparatus. (Hypertension 11: 620-626, 1988) KEYWORDS • vascular smooth muscle • troponin T • tropomyosin • calmodulin-binding protein * calcium T HE contractile process of the muscle is regulated by changes in the sarcoplasmic Ca 2+ concentration. In cardiac and skeletal muscles, actin-myosin interaction is regulated by a specific actin-linked mechanism, the troponin-tropomyosin system.'" 3 Recent studies have suggested that the contraction of vascular smooth muscle is regulated by a Ca 2+ -dependent mechanism in addition to myosin light chain phosphorylation.4 "*The maintenance of vascular smooth muscle tone characterized by a prolonged force production with low energy cost (latch contraction) 7 " 9 could be a major contributor to peripheral vascular resistance. To understand potential myogenic factors responsible for the hypertensive state, the regulatory protein (or proteins) in the second Ca 2+ -dependent mechanism must be identified.We have reported novel proteins with M, values of 33,000 to 35,000 that are present in large amounts in a variety of vertebrate smooth muscles.

show abstract

“…Tropomyosin can exist as either a homo-or heterodimer in the adult heart (␣␣, ␣␤, or ␤␤ but is mostly limited to ␣␣ homodimers). Tropomyosin has been the subject of a range of structure-function studies that utilized elegant biochemical methodologies (282,283,353,360,362,550,888,889). A better understanding of Tm's role under both physiological and pathophysiological conditions in intact cardiac myocytes has been gained through the use of gene transfer technology.…”

Section: Tropomyosinmentioning

confidence: 99%

Designing Heart Performance by Gene Transfer

Davis¹,

Westfall²,

Townsend³

et al. 2008

Physiological Reviews

View full text Add to dashboard Cite

The birth of molecular cardiology can be traced to the development and implementation of high-fidelity genetic approaches for manipulating the heart. Recombinant viral vector-based technology offers a highly effective approach to genetically engineer cardiac muscle in vitro and in vivo. This review highlights discoveries made in cardiac muscle physiology through the use of targeted viral-mediated genetic modification. Here the history of cardiac gene transfer technology and the strengths and limitations of viral and nonviral vectors for gene delivery are reviewed. A comprehensive account is given of the application of gene transfer technology for studying key cardiac muscle targets including Ca2+handling, the sarcomere, the cytoskeleton, and signaling molecules and their posttranslational modifications. The primary objective of this review is to provide a thorough analysis of gene transfer studies for understanding cardiac physiology in health and disease. By comparing results obtained from gene transfer with those obtained from transgenesis and biophysical and biochemical methodologies, this review provides a global view of cardiac structure-function with an eye towards future areas of research. The data presented here serve as a basis for discovery of new therapeutic targets for remediation of acquired and inherited cardiac diseases.

show abstract

Regulation of Muscle Contraction: Binding of Troponin and Its Components to Actin and Tropomyosin

Cited by 107 publications

References 37 publications

Tropomyosin Exon 6b Is Troponin-specific and Required for Correct Acto-myosin Regulation

Tropomyosin Exon 6b Is Troponin-specific and Required for Correct Acto-myosin Regulation

Vascular smooth muscle calponin. A novel troponin T-like protein.

Designing Heart Performance by Gene Transfer

Contact Info

Product

Resources

About