The Journal of Cell Biology, Vol 107, 2199-2212, Copyright © 1988 by The Rockefeller University Press

ARTICLES

Architecture of the sarcomere matrix of skeletal muscle: immunoelectron microscopic evidence that suggests a set of parallel inextensible nebulin filaments anchored at the Z line

K Wang and J Wright
Clayton Foundation Biochemical Institute, Department of Chemistry, University of Texas, at Austin 78712.

Nebulin, a giant myofibrillar protein (600-800 kD) that is abundant (3%) in the sarcomere of a wide range of skeletal muscles, has been proposed as a component of a cytoskeletal matrix that coexists with actin and myosin filaments within the sarcomere. Immunoblot analysis indicates that although polypeptides of similar size are present in cardiac and smooth muscles at low abundance, those proteins show no immunological cross-reactivity with skeletal muscle nebulin. Gel analysis reveals that nebulins in various skeletal muscles of rabbit belong to at least two classes of size variants. A monospecific antibody has been used to localize nebulin by immunoelectron microscopy in a mechanically split rabbit psoas muscle fiber preparation. Labeled split fibers exhibit six pairs of stripes of antibody-imparted transverse densities spaced at 0.1-1.0 micron from the Z line within each sarcomere. These epitopes maintain a fixed distance to the Z line irrespective of sarcomere length and do not exhibit the characteristic elastic stretch-response of titin epitopes within the I band domain. It is proposed that nebulin constitutes a set of inextensible filaments attached at one end to the Z line and that nebulin filaments are in parallel, and not in series, with titin filaments. Thus the skeletal muscle sarcomere may have two sets of nonactomyosin filaments: a set of I segment-linked nebulin filaments and a set of A segment-linked titin filaments. This four-filament sarcomere model raises the possibility that nebulin and titin might act as organizing templates and length- determining factors for actin and myosin respectively.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Kontrogianni-Konstantopoulos, A., Ackermann, M. A., Bowman, A. L., Yap, S. V., Bloch, R. J. (2009). Muscle Giants: Molecular Scaffolds in Sarcomerogenesis. Physiol. Rev. 89: 1217-1267 [Abstract] [Full Text]  
• Ottenheijm, C. A.C., Witt, C. C., Stienen, G. J., Labeit, S., Beggs, A. H., Granzier, H. (2009). Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency. Hum Mol Genet 18: 2359-2369 [Abstract] [Full Text]  
• Gokhin, D. S., Bang, M.-L., Zhang, J., Chen, J., Lieber, R. L. (2009). Reduced thin filament length in nebulin-knockout skeletal muscle alters isometric contractile properties. Am. J. Physiol. Cell Physiol. 296: C1123-C1132 [Abstract] [Full Text]  
• Hanashima, A., Kubokawa, K., Kimura, S. (2009). Characterization of amphioxus nebulin and its similarity to human nebulin. J. Exp. Biol. 212: 668-672 [Abstract] [Full Text]  
• Conover, G. M., Henderson, S. N., Gregorio, C. C. (2009). A Myopathy-linked Desmin Mutation Perturbs Striated Muscle Actin Filament Architecture. Mol. Biol. Cell 20: 834-845 [Abstract] [Full Text]  
• Ottenheijm, C. A. C., Fong, C., Vangheluwe, P., Wuytack, F., Babu, G. J., Periasamy, M., Witt, C. C., Labeit, S., Granzier, H. (2008). Sarcoplasmic reticulum calcium uptake and speed of relaxation are depressed in nebulin-free skeletal muscle. FASEB J. 22: 2912-2919 [Abstract] [Full Text]  
• Pappas, C. T., Bhattacharya, N., Cooper, J. A., Gregorio, C. C. (2008). Nebulin Interacts with CapZ and Regulates Thin Filament Architecture within the Z-Disc. Mol. Biol. Cell 19: 1837-1847 [Abstract] [Full Text]  
• Burgoyne, T., Muhamad, F., Luther, P. K. (2008). Visualization of cardiac muscle thin filaments and measurement of their lengths by electron tomography. Cardiovasc Res 77: 707-712 [Abstract] [Full Text]  
• Bang, M.-L., Li, X., Littlefield, R., Bremner, S., Thor, A., Knowlton, K. U., Lieber, R. L., Chen, J. (2006). Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle. JCB 173: 905-916 [Abstract] [Full Text]  
• McElhinny, A. S., Schwach, C., Valichnac, M., Mount-Patrick, S., Gregorio, C. C. (2005). Nebulin regulates the assembly and lengths of the thin filaments in striated muscle. JCB 170: 947-957 [Abstract] [Full Text]  
• Ogut, O., Hossain, M. M., Jin, J.-P. (2003). Interactions between Nebulin-like Motifs and Thin Filament Regulatory Proteins. J. Biol. Chem. 278: 3089-3097 [Abstract] [Full Text]  
• Pizon, V., Iakovenko, A., van der Ven, P. F. M., Kelly, R., Fatu, C., Furst, D. O., Karsenti, E., Gautel, M. (2002). Transient association of titin and myosin with microtubules in nascent myofibrils directed by the MURF2 RING-finger protein. J. Cell Sci. 115: 4469-4482 [Abstract] [Full Text]  
• Ojima, K., Lin, Z.X., Bang, M.-L., Holtzer, S., Matsuda, R., Labeit, S., Sweeney, H.L., Holtzer, H. (2000). Distinct Families of Z-Line Targeting Modules in the Cooh-Terminal Region of Nebulin. JCB 150: 553-566 [Abstract] [Full Text]  
• Avela, J., Kyrolainen, H., Komi, P. V. (1999). Altered reflex sensitivity after repeated and prolonged passive muscle stretching. J. Appl. Physiol. 86: 1283-1291 [Abstract] [Full Text]  
• Ojima, K, Lin, Z., Zhang, Z., Hijikata, T, Holtzer, S, Labeit, S, Sweeney, H., Holtzer, H (1999). Initiation and maturation of I-Z-I bodies in the growth tips of transfected myotubes. J. Cell Sci. 112: 4101-4112 [Abstract]  
• Huang, J., Forsberg, N. E. (1998). Role of calpain in skeletal-muscle protein degradation. Proc. Natl. Acad. Sci. USA 95: 12100-12105 [Abstract] [Full Text]  
• Wang, K., Knipfer, M., Huang, Q.-Q., van Heerden, A., Hsu, L. C.-L., Gutierrez, G., Quian, X.-L., Stedman, H. (1996). Human Skeletal Muscle Nebulin Sequence Encodes a Blueprint for Thin Filament Architecture. J. Biol. Chem. 271: 4304-4314 [Abstract] [Full Text]  
• Gautel, M, Goulding, D, Bullard, B, Weber, K, Furst, D. (1996). The central Z-disk region of titin is assembled from a novel repeat in variable copy numbers. J. Cell Sci. 109: 2747-2754 [Abstract]  
• Jin, J.-P., Jin, J. P. (1995). Cloned Rat Cardiac Titin Class I and Class II Motifs. J. Biol. Chem. 270: 6908-6916 [Abstract] [Full Text]  
• Ao, X, Lehrer, S. (1995). Phalloidin unzips nebulin from thin filaments in skeletal myofibrils. J. Cell Sci. 108: 3397-3403 [Abstract]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents