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

This Article Full Text Full Text (PDF, 507K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by McElhinny, A. S. Articles by Gregorio, C. C. Search for Related Content PubMed PubMed Citation Articles by McElhinny, A. S. Articles by Gregorio, C. C. Related Collections Related Article Social Bookmarking                      What's this?

¹ Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724
² Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85724
³ Abteilung für Anästhesiologie und Operative Intensiv-Medizin, Universitätsklinikum Mannheim, 68167 Mannheim, Germany
⁴ Graduate School of Agricultural and Life Sciences, University of Tokyo, 113-8657 Tokyo, Japan

Address correspondence to Carol C. Gregorio, Ph.D., Department of Cell Biology and Anatomy, University of Arizona, 1501 N. Campbell Avenue, LSN 455, Tucson, AZ 85724. Tel.: (520) 626-8113. Fax.: (520) 626-2097. E-mail: gregorio{at}u.arizona.edu

The COOH-terminal A168–170 region of the giant sarcomeric protein titin interacts with muscle-specific RING finger-1 (MURF-1). To investigate the functional significance of this interaction, we expressed green fluorescent protein fusion constructs encoding defined fragments of titin's M-line region and MURF-1 in cardiac myocytes. Upon expression of MURF-1 or its central region (containing its titin-binding site), the integrity of titin's M-line region was dramatically disrupted. Disruption of titin's M-line region also resulted in a perturbation of thick filament components, but, surprisingly, not of the NH₂-terminal or I-band regions of titin, the Z-lines, or the thin filaments. This specific phenotype also was caused by the expression of titin A168–170. These data suggest that the interaction of titin with MURF-1 is important for the stability of the sarcomeric M-line region.

MURF-1 also binds to ubiquitin-conjugating enzyme-9 and isopeptidase T-3, enzymes involved in small ubiquitin-related modifier–mediated nuclear import, and with glucocorticoid modulatory element binding protein-1 (GMEB-1), a transcriptional regulator. Consistent with our in vitro binding data implicating MURF-1 with nuclear functions, endogenous MURF-1 also was detected in the nuclei of some myocytes. The dual interactions of MURF-1 with titin and GMEB-1 may link myofibril signaling pathways (perhaps including titin's kinase domain) with muscle gene expression.

Key Words: MURF-1; titin; GMEB-1; cardiac myocyte; SUMO-3

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Article

Clash of the titin

Nicole LeBrasseur
J. Cell Biol. 2002 157: 10. [Full Text] [PDF]

This article has been cited by other articles:

• Qi, J., Chi, L., Labeit, S., Banes, A. J. (2008). Nuclear localization of the titin Z1Z2Zr domain and role in regulating cell proliferation. Am. J. Physiol. Cell Physiol. 295: C975-C985 [Abstract] [Full Text]  
• Nedergaard, A., Vissing, K., Overgaard, K., Kjaer, M., Schjerling, P. (2007). Expression patterns of atrogenic and ubiquitin proteasome component genes with exercise: effect of different loading patterns and repeated exercise bouts. J. Appl. Physiol. 103: 1513-1522 [Abstract] [Full Text]  
• Mrosek, M., Labeit, D., Witt, S., Heerklotz, H., von Castelmur, E., Labeit, S., Mayans, O. (2007). Molecular determinants for the recruitment of the ubiquitin-ligase MuRF-1 onto M-line titin. FASEB J. 21: 1383-1392 [Abstract] [Full Text]  
• Fielitz, J., van Rooij, E., Spencer, J. A., Shelton, J. M., Latif, S., van der Nagel, R., Bezprozvannaya, S., de Windt, L., Richardson, J. A., Bassel-Duby, R., Olson, E. N. (2007). Loss of muscle-specific RING-finger 3 predisposes the heart to cardiac rupture after myocardial infarction. Proc. Natl. Acad. Sci. USA 104: 4377-4382 [Abstract] [Full Text]  
• Seeley, M., Huang, W., Chen, Z., Wolff, W. O., Lin, X., Xu, X. (2007). Depletion of Zebrafish Titin Reduces Cardiac Contractility by Disrupting the Assembly of Z-Discs and A-Bands. Circ. Res. 100: 238-245 [Abstract] [Full Text]  
• Li, P., Waters, R. E., Redfern, S. I., Zhang, M., Mao, L., Annex, B. H., Yan, Z. (2007). Oxidative Phenotype Protects Myofibers from Pathological Insults Induced by Chronic Heart Failure in Mice. Am. J. Pathol. 170: 599-608 [Abstract] [Full Text]  
• Lehti, T. M., Silvennoinen, M., Kivela, R., Kainulainen, H., Komulainen, J. (2007). Effects of streptozotocin-induced diabetes and physical training on gene expression of titin-based stretch-sensing complexes in mouse striated muscle. Am. J. Physiol. Endocrinol. Metab. 292: E533-E542 [Abstract] [Full Text]  
• Salem, M., Kenney, P. B., Rexroad, C. E. 3rd, Yao, J. (2006). Microarray gene expression analysis in atrophying rainbow trout muscle: a unique nonmammalian muscle degradation model. Physiol. Genomics 28: 33-45 [Abstract] [Full Text]  
• Yang, Y., Jemiolo, B., Trappe, S. (2006). Proteolytic mRNA expression in response to acute resistance exercise in human single skeletal muscle fibers. J. Appl. Physiol. 101: 1442-1450 [Abstract] [Full Text]  
• Ma, K., Forbes, J. G., Gutierrez-Cruz, G., Wang, K. (2006). Titin as a Giant Scaffold for Integrating Stress and Src Homology Domain 3-mediated Signaling Pathways: THE CLUSTERING OF NOVEL OVERLAP LIGAND MOTIFS IN THE ELASTIC PEVK SEGMENT. J. Biol. Chem. 281: 27539-27556 [Abstract] [Full Text]  
• Powell, S. R. (2006). The ubiquitin-proteasome system in cardiac physiology and pathology. Am. J. Physiol. Heart Circ. Physiol. 291: H1-H19 [Abstract] [Full Text]  
• Lecker, S. H., Goldberg, A. L., Mitch, W. E. (2006). Protein Degradation by the Ubiquitin-Proteasome Pathway in Normal and Disease States. J. Am. Soc. Nephrol. 17: 1807-1819 [Full Text]  
• Hoshijima, M. (2006). Mechanical stress-strain sensors embedded in cardiac cytoskeleton: Z disk, titin, and associated structures. Am. J. Physiol. Heart Circ. Physiol. 290: H1313-H1325 [Abstract] [Full Text]  
• Huebsch, K. A., Kudryashova, E., Wooley, C. M., Sher, R. B., Seburn, K. L., Spencer, M. J., Cox, G. A. (2005). Mdm muscular dystrophy: interactions with calpain 3 and a novel functional role for titin's N2A domain. Hum Mol Genet 14: 2801-2811 [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]  
• Lange, S., Xiang, F., Yakovenko, A., Vihola, A., Hackman, P., Rostkova, E., Kristensen, J., Brandmeier, B., Franzen, G., Hedberg, B., Gunnarsson, L. G., Hughes, S. M., Marchand, S., Sejersen, T., Richard, I., Edstrom, L., Ehler, E., Udd, B., Gautel, M. (2005). The Kinase Domain of Titin Controls Muscle Gene Expression and Protein Turnover. Science 308: 1599-1603 [Abstract] [Full Text]  
• Udd, B., Vihola, A., Sarparanta, J., Richard, I., Hackman, P. (2005). Titinopathies and extension of the M-line mutation phenotype beyond distal myopathy and LGMD2J. Neurology 64: 636-642 [Abstract] [Full Text]  
• Zhang, Q., Ragnauth, C. D., Skepper, J. N., Worth, N. F., Warren, D. T., Roberts, R. G., Weissberg, P. L., Ellis, J. A., Shanahan, C. M. (2005). Nesprin-2 is a multi-isomeric protein that binds lamin and emerin at the nuclear envelope and forms a subcellular network in skeletal muscle. J. Cell Sci. 118: 673-687 [Abstract] [Full Text]  
• Grater, F., Shen, J., Jiang, H., Gautel, M., Grubmuller, H. (2005). Mechanically Induced Titin Kinase Activation Studied by Force-Probe Molecular Dynamics Simulations. Biophys. J 88: 790-804 [Abstract] [Full Text]  
• Kedar, V., McDonough, H., Arya, R., Li, H.-H., Rockman, H. A., Patterson, C. (2004). Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I. Proc. Natl. Acad. Sci. USA 101: 18135-18140 [Abstract] [Full Text]  
• Arya, R., Kedar, V., Hwang, J. R., McDonough, H., Li, H.-H., Taylor, J., Patterson, C. (2004). Muscle ring finger protein-1 inhibits PKC{epsilon} activation and prevents cardiomyocyte hypertrophy. JCB 167: 1147-1159 [Abstract] [Full Text]  
• Sacheck, J. M., Ohtsuka, A., McLary, S. C., Goldberg, A. L. (2004). IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Am. J. Physiol. Endocrinol. Metab. 287: E591-E601 [Abstract] [Full Text]  
• Sartorelli, V., Fulco, M. (2004). Molecular and Cellular Determinants of Skeletal Muscle Atrophy and Hypertrophy. Sci Signal 2004: re11-re11 [Abstract] [Full Text]  
• Ahuja, P., Perriard, E., Perriard, J.-C., Ehler, E. (2004). Sequential myofibrillar breakdown accompanies mitotic division of mammalian cardiomyocytes. J. Cell Sci. 117: 3295-3306 [Abstract] [Full Text]  
• McElhinny, A. S., Perry, C. N., Witt, C. C., Labeit, S., Gregorio, C. C. (2004). Muscle-specific RING finger-2 (MURF-2) is important for microtubule, intermediate filament and sarcomeric M-line maintenance in striated muscle development. J. Cell Sci. 117: 3175-3188 [Abstract] [Full Text]  
• Granzier, H. L., Labeit, S. (2004). The Giant Protein Titin: A Major Player in Myocardial Mechanics, Signaling, and Disease. Circ. Res. 94: 284-295 [Abstract] [Full Text]  
• Mercer, K. B., Flaherty, D. B., Miller, R. K., Qadota, H., Tinley, T. L., Moerman, D. G., Benian, G. M. (2003). Caenorhabditis elegans UNC-98, a C2H2 Zn Finger Protein, Is a Novel Partner of UNC-97/PINCH in Muscle Adhesion Complexes. Mol. Biol. Cell 14: 2492-2507 [Abstract] [Full Text]  
• Gotthardt, M., Hammer, R. E., Hubner, N., Monti, J., Witt, C. C., McNabb, M., Richardson, J. A., Granzier, H., Labeit, S., Herz, J. (2003). Conditional Expression of Mutant M-line Titins Results in Cardiomyopathy with Altered Sarcomere Structure. J. Biol. Chem. 278: 6059-6065 [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]  

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