Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jul 1;88(13):5739–5743. doi: 10.1073/pnas.88.13.5739

Parallel inhibition of active force and relaxed fiber stiffness in skeletal muscle by caldesmon: implications for the pathway to force generation.

B Brenner 1, L C Yu 1, J M Chalovich 1
PMCID: PMC51953  PMID: 2062853

Abstract

In recent hypotheses on muscle contraction, myosin cross-bridges cycle between two types of actin-bound configuration. These two configurations differ greatly in the stability of their actin-myosin complexes ("weak-binding" vs. "strong-binding"), and force generation or movement is the result of structural changes associated with the transition from the weak-binding (preforce generating) configuration to strong-binding (force producing) configuration [cf. Eisenberg, E. & Hill, T. L. (1985) Science 227, 999-1006]. Specifically, in this concept, the main force-generating states are only accessible after initial cross-bridge attachment in a weak-binding configuration. It has been shown that strong and weak cross-bridge attachment can occur in muscle fibers [Brenner, B., Schoenberg, M., Chalovich, J. M., Greene, L. E. & Eisenberg, E. (1982) Proc. Natl. Acad. Sci. USA 79, 7288-7291]. However, there has been no evidence that attachment in the weak-binding states represents an essential step leading to force generation. It is shown here that caldesmon can be used to selectively inhibit attachment of weak-binding cross-bridges in skeletal muscle. Such inhibition causes a parallel decrease in active force, while the kinetics of cross-bridge turnover are unchanged by this procedure. This suggests that (i) cross-bridge attachment in the weak-binding states is specific and (ii) force production can only occur after cross-bridges have first attached to actin in a weakly bound, nonforce-generating configuration.

Full text

PDF
5739

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams S., DasGupta G., Chalovich J. M., Reisler E. Immunochemical evidence for the binding of caldesmon to the NH2-terminal segment of actin. J Biol Chem. 1990 Nov 15;265(32):19652–19657. [PubMed] [Google Scholar]
  2. Bartegi A., Fattoum A., Kassab R. Cross-linking of smooth muscle caldesmon to the NH2-terminal region of skeletal F-actin. J Biol Chem. 1990 Feb 5;265(4):2231–2237. [PubMed] [Google Scholar]
  3. Bremel R. D., Weber A. Cooperation within actin filament in vertebrate skeletal muscle. Nat New Biol. 1972 Jul 26;238(82):97–101. doi: 10.1038/newbio238097a0. [DOI] [PubMed] [Google Scholar]
  4. Brenner B., Chalovich J. M., Greene L. E., Eisenberg E., Schoenberg M. Stiffness of skinned rabbit psoas fibers in MgATP and MgPPi solution. Biophys J. 1986 Oct;50(4):685–691. doi: 10.1016/S0006-3495(86)83509-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brenner B. Effect of Ca2+ on cross-bridge turnover kinetics in skinned single rabbit psoas fibers: implications for regulation of muscle contraction. Proc Natl Acad Sci U S A. 1988 May;85(9):3265–3269. doi: 10.1073/pnas.85.9.3265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brenner B., Eisenberg E. Rate of force generation in muscle: correlation with actomyosin ATPase activity in solution. Proc Natl Acad Sci U S A. 1986 May;83(10):3542–3546. doi: 10.1073/pnas.83.10.3542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brenner B. Mechanical and structural approaches to correlation of cross-bridge action in muscle with actomyosin ATPase in solution. Annu Rev Physiol. 1987;49:655–672. doi: 10.1146/annurev.ph.49.030187.003255. [DOI] [PubMed] [Google Scholar]
  8. Brenner B., Schoenberg M., Chalovich J. M., Greene L. E., Eisenberg E. Evidence for cross-bridge attachment in relaxed muscle at low ionic strength. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7288–7291. doi: 10.1073/pnas.79.23.7288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brenner B. Technique for stabilizing the striation pattern in maximally calcium-activated skinned rabbit psoas fibers. Biophys J. 1983 Jan;41(1):99–102. doi: 10.1016/S0006-3495(83)84411-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brenner B., Yu L. C., Greene L. E., Eisenberg E., Schoenberg M. Ca2+-sensitive cross-bridge dissociation in the presence of magnesium pyrophosphate in skinned rabbit psoas fibers. Biophys J. 1986 Dec;50(6):1101–1108. doi: 10.1016/S0006-3495(86)83554-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Brenner B., Yu L. C., Podolsky R. J. X-ray diffraction evidence for cross-bridge formation in relaxed muscle fibers at various ionic strengths. Biophys J. 1984 Sep;46(3):299–306. doi: 10.1016/S0006-3495(84)84026-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bryan J., Imai M., Lee R., Moore P., Cook R. G., Lin W. G. Cloning and expression of a smooth muscle caldesmon. J Biol Chem. 1989 Aug 15;264(23):13873–13879. [PubMed] [Google Scholar]
  13. Chalovich J. M. Caldesmon and thin-filament regulation of muscle contraction. Cell Biophys. 1988 Jan-Jun;12:73–85. doi: 10.1007/BF02918351. [DOI] [PubMed] [Google Scholar]
  14. Chalovich J. M., Chock P. B., Eisenberg E. Mechanism of action of troponin . tropomyosin. Inhibition of actomyosin ATPase activity without inhibition of myosin binding to actin. J Biol Chem. 1981 Jan 25;256(2):575–578. [PMC free article] [PubMed] [Google Scholar]
  15. Chalovich J. M., Cornelius P., Benson C. E. Caldesmon inhibits skeletal actomyosin subfragment-1 ATPase activity and the binding of myosin subfragment-1 to actin. J Biol Chem. 1987 Apr 25;262(12):5711–5716. [PubMed] [Google Scholar]
  16. Chalovich J. M., Eisenberg E. Inhibition of actomyosin ATPase activity by troponin-tropomyosin without blocking the binding of myosin to actin. J Biol Chem. 1982 Mar 10;257(5):2432–2437. [PMC free article] [PubMed] [Google Scholar]
  17. Chalovich J. M., Eisenberg E. The effect of troponin-tropomyosin on the binding of heavy meromyosin to actin in the presence of ATP. J Biol Chem. 1986 Apr 15;261(11):5088–5093. [PMC free article] [PubMed] [Google Scholar]
  18. Chalovich J. M., Greene L. E., Eisenberg E. Crosslinked myosin subfragment 1: a stable analogue of the subfragment-1.ATP complex. Proc Natl Acad Sci U S A. 1983 Aug;80(16):4909–4913. doi: 10.1073/pnas.80.16.4909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Eisenberg E., Hill T. L. Muscle contraction and free energy transduction in biological systems. Science. 1985 Mar 1;227(4690):999–1006. doi: 10.1126/science.3156404. [DOI] [PubMed] [Google Scholar]
  20. Ford L. E., Huxley A. F., Simmons R. M. Tension transients during the rise of tetanic tension in frog muscle fibres. J Physiol. 1986 Mar;372:595–609. doi: 10.1113/jphysiol.1986.sp016027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Greene L. E., Eisenberg E. Cooperative binding of myosin subfragment-1 to the actin-troponin-tropomyosin complex. Proc Natl Acad Sci U S A. 1980 May;77(5):2616–2620. doi: 10.1073/pnas.77.5.2616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Greene L. E., Eisenberg E. Dissociation of the actin.subfragment 1 complex by adenyl-5'-yl imidodiphosphate, ADP, and PPi. J Biol Chem. 1980 Jan 25;255(2):543–548. [PubMed] [Google Scholar]
  23. Greene L. E., Williams D. L., Jr, Eisenberg E. Regulation of actomyosin ATPase activity by troponin-tropomyosin: effect of the binding of the myosin subfragment 1 (S-1).ATP complex. Proc Natl Acad Sci U S A. 1987 May;84(10):3102–3106. doi: 10.1073/pnas.84.10.3102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. HUXLEY A. F. Muscle structure and theories of contraction. Prog Biophys Biophys Chem. 1957;7:255–318. [PubMed] [Google Scholar]
  25. Hemric M. E., Chalovich J. M. Effect of caldesmon on the ATPase activity and the binding of smooth and skeletal myosin subfragments to actin. J Biol Chem. 1988 Feb 5;263(4):1878–1885. [PubMed] [Google Scholar]
  26. Hibberd M. G., Trentham D. R. Relationships between chemical and mechanical events during muscular contraction. Annu Rev Biophys Biophys Chem. 1986;15:119–161. doi: 10.1146/annurev.bb.15.060186.001003. [DOI] [PubMed] [Google Scholar]
  27. Highsmith S. The effects of temperature and salts on myosin subfragment-1 and F-actin association. Arch Biochem Biophys. 1977 Apr 30;180(2):404–408. doi: 10.1016/0003-9861(77)90054-6. [DOI] [PubMed] [Google Scholar]
  28. Hill T. L. Theoretical formalism for the sliding filament model of contraction of striated muscle. Part I. Prog Biophys Mol Biol. 1974;28:267–340. doi: 10.1016/0079-6107(74)90020-0. [DOI] [PubMed] [Google Scholar]
  29. Huxley H. E., Kress M. Crossbridge behaviour during muscle contraction. J Muscle Res Cell Motil. 1985 Apr;6(2):153–161. doi: 10.1007/BF00713057. [DOI] [PubMed] [Google Scholar]
  30. Huxley H. E. Structural difference between resting and rigor muscle; evidence from intensity changes in the lowangle equatorial x-ray diagram. J Mol Biol. 1968 Nov 14;37(3):507–520. doi: 10.1016/0022-2836(68)90118-6. [DOI] [PubMed] [Google Scholar]
  31. Levine B. A., Moir A. J., Audemard E., Mornet D., Patchell V. B., Perry S. V. Structural study of gizzard caldesmon and its interaction with actin. Binding involves residues of actin also recognised by myosin subfragment 1. Eur J Biochem. 1990 Nov 13;193(3):687–696. doi: 10.1111/j.1432-1033.1990.tb19388.x. [DOI] [PubMed] [Google Scholar]
  32. Lymn R. W., Taylor E. W. Mechanism of adenosine triphosphate hydrolysis by actomyosin. Biochemistry. 1971 Dec 7;10(25):4617–4624. doi: 10.1021/bi00801a004. [DOI] [PubMed] [Google Scholar]
  33. Lynch W. P., Riseman V. M., Bretscher A. Smooth muscle caldesmon is an extended flexible monomeric protein in solution that can readily undergo reversible intra- and intermolecular sulfhydryl cross-linking. A mechanism for caldesmon's F-actin bundling activity. J Biol Chem. 1987 May 25;262(15):7429–7437. [PubMed] [Google Scholar]
  34. Margossian S. S., Lowey S. Interaction of myosin subfragments with F-actin. Biochemistry. 1978 Dec 12;17(25):5431–5439. doi: 10.1021/bi00618a017. [DOI] [PubMed] [Google Scholar]
  35. Marston S. B. The rates of formation and dissociation of actin-myosin complexes. Effects of solvent, temperature, nucleotide binding and head-head interactions. Biochem J. 1982 May 1;203(2):453–460. doi: 10.1042/bj2030453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Marston S., Weber A. The dissociation constant of the actin-heavy meromyosin subfragment-1 complex. Biochemistry. 1975 Aug 26;14(17):3868–3873. doi: 10.1021/bi00688a021. [DOI] [PubMed] [Google Scholar]
  37. Parry D. A., Squire J. M. Structural role of tropomyosin in muscle regulation: analysis of the x-ray diffraction patterns from relaxed and contracting muscles. J Mol Biol. 1973 Mar 25;75(1):33–55. doi: 10.1016/0022-2836(73)90527-5. [DOI] [PubMed] [Google Scholar]
  38. Pringle J. W. The contractile mechanism of insect fibrillar muscle. Prog Biophys Mol Biol. 1967;17:1–60. doi: 10.1016/0079-6107(67)90003-x. [DOI] [PubMed] [Google Scholar]
  39. Proceedings of the Contractility Sub-group of the American Biophysical Society. Mechanical approaches to the elucidation of the crossbridge cycle. Baltimore, 24-28 February 1985. Abstracts. J Muscle Res Cell Motil. 1985 Oct;6(5):659–668. doi: 10.1007/BF00711919. [DOI] [PubMed] [Google Scholar]
  40. Riseman V. M., Lynch W. P., Nefsky B., Bretscher A. The calmodulin and F-actin binding sites of smooth muscle caldesmon lie in the carboxyl-terminal domain whereas the molecular weight heterogeneity lies in the middle of the molecule. J Biol Chem. 1989 Feb 15;264(5):2869–2875. [PubMed] [Google Scholar]
  41. Rosenfeld S. S., Taylor E. W. The ATPase mechanism of skeletal and smooth muscle acto-subfragment 1. J Biol Chem. 1984 Oct 10;259(19):11908–11919. [PubMed] [Google Scholar]
  42. Sleep J. A., Hutton R. L. Actin mediated release of ATP from a myosin-ATP complex. Biochemistry. 1978 Dec 12;17(25):5423–5430. doi: 10.1021/bi00618a016. [DOI] [PubMed] [Google Scholar]
  43. Stein L. A., Schwarz R. P., Jr, Chock P. B., Eisenberg E. Mechanism of actomyosin adenosine triphosphatase. Evidence that adenosine 5'-triphosphate hydrolysis can occur without dissociation of the actomyosin complex. Biochemistry. 1979 Sep 4;18(18):3895–3909. doi: 10.1021/bi00585a009. [DOI] [PubMed] [Google Scholar]
  44. Stein L. A. The modeling of the actomyosin subfragment-1 ATPase activity. Cell Biophys. 1988 Jan-Jun;12:29–58. doi: 10.1007/BF02918349. [DOI] [PubMed] [Google Scholar]
  45. Sutherland C., Walsh M. P. Phosphorylation of caldesmon prevents its interaction with smooth muscle myosin. J Biol Chem. 1989 Jan 5;264(1):578–583. [PubMed] [Google Scholar]
  46. Szpacenko A., Dabrowska R. Functional domain of caldesmon. FEBS Lett. 1986 Jul 7;202(2):182–186. doi: 10.1016/0014-5793(86)80683-4. [DOI] [PubMed] [Google Scholar]
  47. Velaz L., Hemric M. E., Benson C. E., Chalovich J. M. The binding of caldesmon to actin and its effect on the ATPase activity of soluble myosin subfragments in the presence and absence of tropomyosin. J Biol Chem. 1989 Jun 5;264(16):9602–9610. [PubMed] [Google Scholar]
  48. Velaz L., Ingraham R. H., Chalovich J. M. Dissociation of the effect of caldesmon on the ATPase activity and on the binding of smooth heavy meromyosin to actin by partial digestion of caldesmon. J Biol Chem. 1990 Feb 15;265(5):2929–2934. [PubMed] [Google Scholar]
  49. Wagner P. D. Effect of skeletal muscle myosin light chain 2 on the Ca2+-sensitive interaction of myosin and heavy meromyosin with regulated actin. Biochemistry. 1984 Dec 4;23(25):5950–5956. doi: 10.1021/bi00320a010. [DOI] [PubMed] [Google Scholar]
  50. Wagner P. D., Giniger E. Calcium-sensitive binding of heavy meromyosin to regulated actin in the presence of ATP. J Biol Chem. 1981 Dec 25;256(24):12647–12650. [PubMed] [Google Scholar]
  51. White H. D., Taylor E. W. Energetics and mechanism of actomyosin adenosine triphosphatase. Biochemistry. 1976 Dec 28;15(26):5818–5826. doi: 10.1021/bi00671a020. [DOI] [PubMed] [Google Scholar]
  52. White H. D., Taylor E. W. Energetics and mechanism of actomyosin adenosine triphosphatase. Biochemistry. 1976 Dec 28;15(26):5818–5826. doi: 10.1021/bi00671a020. [DOI] [PubMed] [Google Scholar]
  53. Yu L. C. Analysis of equatorial x-ray diffraction patterns from skeletal muscle. Biophys J. 1989 Mar;55(3):433–440. doi: 10.1016/S0006-3495(89)82837-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Yu L. C., Brenner B. Structures of actomyosin crossbridges in relaxed and rigor muscle fibers. Biophys J. 1989 Mar;55(3):441–453. doi: 10.1016/S0006-3495(89)82838-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES