|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Journal of Cell Science, Vol 109, Issue 1 101-111, Copyright © 1996 by Company of Biologists
JOURNAL ARTICLES |
R Gilbert, MG Kelly, T Mikawa and DA Fischman
Department of Cell Biology and Anatomy, Cornell University Medical College, New York, NY 10021, USA.
Myosin binding protein-C (MyBP-C), also known as C-protein, is a major constituent of the thick filaments of vertebrate striated muscles. The protein, approximately 130 kDa, consists of a series of 10 globular motifs (numbered I to X) each of approximately 90-100 amino acids, bearing resemblance to the C2-set of immunoglobins (Ig C2) and to the fibronectin type III (FnIII) motifs. Using pure preparations of myosin and MyBP-C, it has been demonstrated that the major myosin binding domain of MyBP-C resides within the C-terminal Ig C2 motif (motif X). However, in the context of the in vivo thick filament, it is uncertain if the latter domain is sufficient to target MyBP-C correctly to the A-band or if other regions of the molecule are required for this process. To answer this question, cultures of skeletal muscle myoblasts were transfected with expression plasmids encoding seven truncation mutants of MyBP-C, and their targeting to the A-band investigated by immunofluorescence microscopy. To distinguish the recombinant proteins from endogenous MyBP-C, a myc epitope was inserted at each amino terminus. Recombinant MyBP-C exhibited an identical distribution in the sarcomere to that of native MyBP-C; i.e. it was found exclusively in the C-zone of the A-band. A mutant encoding the C-terminal 372 amino acids, but lacking motifs I-VI (termed delta 1-6), also targeted correctly to the A-band. This fragment, which is composed of two Ig C2 and two FnIII motifs, was the minimal protein fragment required for correct A-band incorporation. Larger amino-terminal deletions or deletion of motif X, the myosin binding domain, abolished all localization to the A-band. One construct (delta 10) lacking only motif X strongly inhibited myofibril assembly. We conclude that the myosin binding domain of MyBP-C, although essential, is not sufficient for correct incorporation into the A-band and that motifs VII to IX are required for this process. The data suggest a topological model in which MyBP-C is associated with the thick filament through its C terminus.
This article has been cited by other articles:
|
|
 |
|
  T. Nagayama, E. Takimoto, S. Sadayappan, J. O. Mudd, J.G. Seidman, J. Robbins, and D. A. Kass Control of In Vivo Contraction/Relaxation Kinetics by Myosin Binding Protein C: Protein Kinase A Phosphorylation Dependent and Independent Regulation Circulation, November 20, 2007; 116(21): 2399 - 2408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Brickson, D. P. Fitzsimons, L. Pereira, T. Hacker, H. Valdivia, and R. L. Moss In vivo left ventricular functional capacity is compromised in cMyBP-C null mice Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1747 - H1754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Stelzer, S. B. Dunning, and R. L. Moss Ablation of Cardiac Myosin-Binding Protein-C Accelerates Stretch Activation in Murine Skinned Myocardium Circ. Res., May 12, 2006; 98(9): 1212 - 1218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. McGrath, D. L. Cottle, M.-A. Nguyen, J. M. Dyson, I. D. Coghill, P. A. Robinson, M. Holdsworth, B. S. Cowling, E. C. Hardeman, C. A. Mitchell, et al. Four and a Half LIM Protein 1 Binds Myosin-binding Protein C and Regulates Myosin Filament Formation and Sarcomere Assembly J. Biol. Chem., March 17, 2006; 281(11): 7666 - 7683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Palmer, T. Noguchi, Y. Wang, J. R. Heim, N. R. Alpert, P. G. Burgon, C. E. Seidman, J.G. Seidman, D. W. Maughan, and M. M. LeWinter Effect of Cardiac Myosin Binding Protein-C on Mechanoenergetics in Mouse Myocardium Circ. Res., June 25, 2004; 94(12): 1615 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Flashman, C. Redwood, J. Moolman-Smook, and H. Watkins Cardiac Myosin Binding Protein C: Its Role in Physiology and Disease Circ. Res., May 28, 2004; 94(10): 1279 - 1289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Palmer, D. Georgakopoulos, P. M. Janssen, Y. Wang, N. R. Alpert, D. F. Belardi, S. P. Harris, R. L. Moss, P. G. Burgon, C. E. Seidman, et al. Role of Cardiac Myosin Binding Protein C in Sustaining Left Ventricular Systolic Stiffening Circ. Res., May 14, 2004; 94(9): 1249 - 1255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Kulikovskaya, G. McClellan, J. Flavigny, L. Carrier, and S. Winegrad Effect of MyBP-C Binding to Actin on Contractility in Heart Muscle J. Gen. Physiol., November 24, 2003; 122(6): 761 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. S. Korte, K. S. McDonald, S. P. Harris, and R. L. Moss Loaded Shortening, Power Output, and Rate of Force Redevelopment Are Increased With Knockout of Cardiac Myosin Binding Protein-C Circ. Res., October 17, 2003; 93(8): 752 - 758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Sato, T. Kawakami, A. Nakayama, H. Suzuki, H. Kasahara, and T. Obinata A Novel Variant of Cardiac Myosin-binding Protein-C That Is Unable to Assemble into Sarcomeres Is Expressed in the Aged Mouse Atrium Mol. Biol. Cell, August 1, 2003; 14(8): 3180 - 3191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fatkin and R. M. Graham Molecular Mechanisms of Inherited Cardiomyopathies Physiol Rev, October 1, 2002; 82(4): 945 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Welikson and D. A. Fischman The C-terminal IgI domains of myosin-binding proteins C and H (MyBP-C and MyBP-H) are both necessary and sufficient for the intracellular crosslinking of sarcomeric myosin in transfected non-muscle cells J. Cell Sci., January 9, 2002; 115(17): 3517 - 3526. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Reedy, B. Bullard, and J. O. Vigoreaux Flightin Is Essential for Thick Filament Assembly and Sarcomere Stability in Drosophila Flight Muscles J. Cell Biol., December 27, 2000; 151(7): 1483 - 1500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. van der Ven, J. Bartsch, M Gautel, H Jockusch, and D. Furst A functional knock-out of titin results in defective myofibril assembly J. Cell Sci., January 4, 2000; 113(8): 1405 - 1414. [Abstract] [PDF]
|
|
|
|
|
|
Q. Yang, A. Sanbe, H. Osinska, T. E. Hewett, R. Klevitsky, and J. Robbins In Vivo Modeling of Myosin Binding Protein C Familial Hypertrophic Cardiomyopathy Circ. Res., October 29, 1999; 85(9): 841 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Redwood, J. C. Moolman-Smook, and H. Watkins Properties of mutant contractile proteins that cause hypertrophic cardiomyopathy Cardiovasc Res, October 1, 1999; 44(1): 20 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Winegrad Cardiac Myosin Binding Protein C Circ. Res., May 28, 1999; 84(10): 1117 - 1126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Auerbach, S. Bantle, S. Keller, V. Hinderling, M. Leu, E. Ehler, and J.-C. Perriard Different Domains of the M-Band Protein Myomesin Are Involved in Myosin Binding and M-Band Targeting Mol. Biol. Cell, May 1, 1999; 10(5): 1297 - 1308. [Abstract] [Full Text]
|
|
|
|
|
|
A Almenar-Queralt, C. Gregorio, and V. Fowler Tropomodulin assembles early in myofibrillogenesis in chick skeletal muscle: evidence that thin filaments rearrange to form striated myofibrils J. Cell Sci., January 4, 1999; 112(8): 1111 - 1123. [Abstract] [PDF]
|
|
|
|
|
|
R Gilbert, J. Cohen, S Pardo, A Basu, and D. Fischman Identification of the A-band localization domain of myosin binding proteins C and H (MyBP-C, MyBP-H) in skeletal muscle J. Cell Sci., January 1, 1999; 112(1): 69 - 79. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Niimura, L. L. Bachinski, S. Sangwatanaroj, H. Watkins, A. E. Chudley, W. McKenna, A. Kristinsson, R. Roberts, M. Sole, B. J. Maron, et al. Mutations in the Gene for Cardiac Myosin-Binding Protein C and Late-Onset Familial Hypertrophic Cardiomyopathy N. Engl. J. Med., April 30, 1998; 338(18): 1248 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Silver, A. V. Vorotnikov, D. M. Watterson, V. P. Shirinsky, and J. R. Sellers Sites of Interaction between Kinase-related Protein and Smooth Muscle Myosin J. Biol. Chem., October 3, 1997; 272(40): 25353 - 25359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. N. Alyonycheva, T. Mikawa, F. C. Reinach, and D. A. Fischman Isoform-specific Interaction of the Myosin-binding Proteins (MyBPs) with Skeletal and Cardiac Myosin Is a Property of the C-terminal Immunoglobulin Domain J. Biol. Chem., August 15, 1997; 272(33): 20866 - 20872. [Abstract] [Full Text] [PDF]
|
|
