Alterations at the Intercalated Disk Associated with the Absence of Muscle LIM Protein

doi:10.1083/jcb.153.4.763

Get More Out of Microscopy - Agilent iMIC 2000

Published online 14 May 2001. doi:10.1083/jcb.153.4.763

This Article

Full Text

PDF (Full Text)

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 Ehler, E.

Articles by Perriard, J.-C.

Search for Related Content

PubMed

PubMed Citation

Articles by Ehler, E.

Articles by Perriard, J.-C.

Pubmed/NCBI databases

Substance via MeSH

Social Bookmarking

What's this?

© The Rockefeller University Press, 0021-9525/2001/5/763/ $5.00
The Journal of Cell Biology, Volume 153, Number 4, May 14, 2001 763-772

Original Article

Alterations at the Intercalated Disk Associated with the Absence of Muscle LIM Protein

Elisabeth Ehler^a, Robert Horowits^b, Christian Zuppinger^a, Robert L. Price^c, Evelyne Perriard^a, Martin Leu^a, Pico Caroni^d, Mark Sussman^e, Hans M. Eppenberger^a, and Jean-Claude Perriard^a
^a Institute of Cell Biology, Swiss Federal Institute of Technology, CH-8093 Zürich, Switzerland
^b Laboratory of Physical Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892
^c Department of Developmental Biology and Anatomy, University of South Carolina, Columbia, South Carolina 29208
^d Friedrich Miescher Institute Basel, CH-4002 Basel, Switzerland
^e The Children's Hospital and Research Foundation, Cincinnati, Ohio 45229

Correspondence to: Jean-Claude Perriard, Institute of Cell Biology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland. Tel:41-1-6333359 Fax:41-1-6331069 E-mail:jcp{at}cell.biol.ethz.ch.

In this study, we investigated cardiomyocyte cytoarchitecturein a mouse model for dilated cardiomyopathy (DCM), the muscleLIM protein (MLP) knockout mouse and substantiated several observationsin a second DCM model, the tropomodulin-overexpressing transgenic(TOT) mouse. Freshly isolated cardiomyocytes from both strainsare characterized by a more irregular shape compared with wild-typecells. Alterations are observed at the intercalated disks, thespecialized areas of mechanical coupling between cardiomyocytes,whereas the subcellular organization of contractile proteinsin the sarcomeres of MLP knockout mice appears unchanged. Distinctparts of the intercalated disks are affected differently. Componentsfrom the adherens junctions are upregulated, desmosomal proteinsare unchanged, and gap junction proteins are downregulated.In addition, the expression of N-RAP, a LIM domain– containingprotein located at the intercalated disks, is upregulated inMLP knockout as well as in TOT mice. Detailed analysis of intercalateddisk composition during postnatal development reveals that anupregulation of N-RAP expression might serve as an early markerfor the development of DCM. Altered expression levels of cytoskeletalproteins (either the lack of MLP or an increased expressionof tropomodulin) apparently lead to impaired function of themyofibrillar apparatus and to physiological stress that ultimatelyresults in DCM and is accompanied by an altered appearance andcomposition of the intercalated disks.

Key Words: dilated cardiomyopathy, N-RAP, tropomodulin, adherens junction,gap junction

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

This article has been cited by other articles:

Geier, C., Gehmlich, K., Ehler, E., Hassfeld, S., Perrot, A., Hayess, K., Cardim, N., Wenzel, K., Erdmann, B., Krackhardt, F., Posch, M. G., Bublak, A., Nagele, H., Scheffold, T., Dietz, R., Chien, K. R., Spuler, S., Furst, D. O., Nurnberg, P., Ozcelik, C. (2008). Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy. Hum Mol Genet 17: 2753-2765 [Abstract] [Full Text]
Gustafson-Wagner, E. A., Sinn, H. W., Chen, Y.-L., Wang, D.-Z., Reiter, R. S., Lin, J. L.-C., Yang, B., Williamson, R. A., Chen, J., Lin, C.-I., Lin, J. J.-C. (2007). Loss of mXin{alpha}, an intercalated disk protein, results in cardiac hypertrophy and cardiomyopathy with conduction defects. Am. J. Physiol. Heart Circ. Physiol. 293: H2680-H2692 [Abstract] [Full Text]
Clark, K. A., Bland, J. M., Beckerle, M. C. (2007). The Drosophila muscle LIM protein, Mlp84B, cooperates with D-titin to maintain muscle structural integrity. J. Cell Sci. 120: 2066-2077 [Abstract] [Full Text]
Sheikh, F., Chen, Y., Liang, X., Hirschy, A., Stenbit, A. E., Gu, Y., Dalton, N. D., Yajima, T., Lu, Y., Knowlton, K. U., Peterson, K. L., Perriard, J.-C., Chen, J. (2006). {alpha}-E-Catenin Inactivation Disrupts the Cardiomyocyte Adherens Junction, Resulting in Cardiomyopathy and Susceptibility to Wall Rupture. Circulation 114: 1046-1055 [Abstract] [Full Text]
Wilding, J. R., Joubert, F., de Araujo, C., Fortin, D., Novotova, M., Veksler, V., Ventura-Clapier, R. (2006). Altered energy transfer from mitochondria to sarcoplasmic reticulum after cytoarchitectural perturbations in mice hearts. J. Physiol. 575: 191-200 [Abstract] [Full Text]
Mahmoodzadeh, S., Eder, S., Nordmeyer, J., Ehler, E., Huber, O., Martus, P., Weiske, J., Pregla, R., Hetzer, R., Regitz-Zagrosek, V. (2006). Estrogen receptor alpha up-regulation and redistribution in human heart failure. FASEB J. 20: 926-934 [Abstract] [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]
Bennett, P. M., Maggs, A. M., Baines, A. J., Pinder, J. C. (2006). The Transitional Junction: A New Functional Subcellular Domain at the Intercalated Disc. Mol. Biol. Cell 17: 2091-2100 [Abstract] [Full Text]
Parlakian, A., Charvet, C., Escoubet, B., Mericskay, M., Molkentin, J. D., Gary-Bobo, G., De Windt, L. J., Ludosky, M.-A., Paulin, D., Daegelen, D., Tuil, D., Li, Z. (2005). Temporally Controlled Onset of Dilated Cardiomyopathy Through Disruption of the SRF Gene in Adult Heart. Circulation 112: 2930-2939 [Abstract] [Full Text]
Barash, I. A., Mathew, L., Lahey, M., Greaser, M. L., Lieber, R. L. (2005). Muscle LIM protein plays both structural and functional roles in skeletal muscle. Am. J. Physiol. Cell Physiol. 289: C1312-C1320 [Abstract] [Full Text]
Forster, C., Kietz, S., Hultenby, K., Warner, M., Gustafsson, J.-A. (2004). Characterization of the ER{beta}-/-mouse heart. Proc. Natl. Acad. Sci. USA 101: 14234-14239 [Abstract] [Full Text]
Zemljic-Harpf, A. E., Ponrartana, S., Avalos, R. T., Jordan, M. C., Roos, K. P., Dalton, N. D., Phan, V. Q., Adamson, E. D., Ross, R. S. (2004). Heterozygous Inactivation of the Vinculin Gene Predisposes to Stress-Induced Cardiomyopathy. Am. J. Pathol. 165: 1033-1044 [Abstract] [Full Text]
Barash, I. A., Mathew, L., Ryan, A. F., Chen, J., Lieber, R. L. (2004). Rapid muscle-specific gene expression changes after a single bout of eccentric contractions in the mouse. Am. J. Physiol. Cell Physiol. 286: C355-C364 [Abstract] [Full Text]
Fritz-Six, K. L., Cox, P. R., Fischer, R. S., Xu, B., Gregorio, C. C., Zoghbi, H. Y., Fowler, V. M. (2003). Aberrant myofibril assembly in tropomodulin1 null mice leads to aborted heart development and embryonic lethality. J. Cell Biol. 163: 1033-1044 [Abstract] [Full Text]
Lu, S., Carroll, S. L., Herrera, A. H., Ozanne, B., Horowits, R. (2003). New N-RAP-binding partners {alpha}-actinin, filamin and Krp1 detected by yeast two-hybrid screening: implications for myofibril assembly. J. Cell Sci. 116: 2169-2178 [Abstract] [Full Text]
Lange, S., Auerbach, D., McLoughlin, P., Perriard, E., Schafer, B. W., Perriard, J.-C., Ehler, E. (2003). Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2. J. Cell Sci. 115: 4925-4936 [Abstract] [Full Text]
Gutstein, D. E., Liu, F.-y., Meyers, M. B., Choo, A., Fishman, G. I. (2003). The organization of adherens junctions and desmosomes at the cardiac intercalated disc is independent of gap junctions. J. Cell Sci. 116: 875-885 [Abstract] [Full Text]
Knoll, R., Hoshijima, M., Chien, K.R. (2002). Z-line proteins: implications for additional functions. Eur Heart J Suppl 4: I13-I17 [Abstract]
Welch, S., Plank, D., Witt, S., Glascock, B., Schaefer, E., Chimenti, S., Andreoli, A. M., Limana, F., Leri, A., Kajstura, J., Anversa, P., Sussman, M. A. (2002). Cardiac-Specific IGF-1 Expression Attenuates Dilated Cardiomyopathy in Tropomodulin-Overexpressing Transgenic Mice. Circ. Res. 90: 641-648 [Abstract] [Full Text]
Fielitz, J., Dendorfer, A., Pregla, R., Ehler, E., Zurbrugg, H. R., Bartunek, J., Hetzer, R., Regitz-Zagrosek, V. (2002). Neutral Endopeptidase Is Activated in Cardiomyocytes in Human Aortic Valve Stenosis and Heart Failure. Circulation 105: 286-289 [Abstract] [Full Text]
Henderson, J. R., Brown, D., Richardson, J. A., Olson, E. N., Beckerle, M. C. (2002). Expression of the Gene Encoding the LIM Protein CRP2: A Developmental Profile. J. Histochem. Cytochem. 50: 107-112 [Abstract] [Full Text]
Carroll, S. L., Herrera, A. H., Horowits, R. (2001). Targeting and functional role of N-RAP, a nebulin-related LIM protein, during myofibril assembly in cultured chick cardiomyocytes. J. Cell Sci. 114: 4229-4238 [Abstract] [Full Text]
Welch, S., Plank, D., Witt, S., Glascock, B., Schaefer, E., Chimenti, S., Andreoli, A. M., Limana, F., Leri, A., Kajstura, J., Anversa, P., Sussman, M. A. (2002). Cardiac-Specific IGF-1 Expression Attenuates Dilated Cardiomyopathy in Tropomodulin-Overexpressing Transgenic Mice. Circ. Res. 90: 641-648 [Abstract] [Full Text]