Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy

Schroen B, Leenders JJ, van Erk A, Bertrand AT, van Loon M, van Leeuwen RE, Kubben N, Duisters RF, Schellings MW, Janssen BJ, Debets JJ, et al. (2007)
Journal of Experimental Medicine 204(5): 1227-1235.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Schroen, Blanche; Leenders, Joost J.; van Erk, Arie; Bertrand, Anne T.; van Loon, Mirjam; van Leeuwen, Rick E.; Kubben, Nard; Duisters, Rudy F.; Schellings, Mark W.; Janssen, Ben J.; Debets, Jacques J.; Schwake, MichaelUniBi
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Abstract / Bemerkung
The intercalated disc (ID) of cardiac myocytes is emerging as a crucial structure in the heart. Loss of ID proteins like N-cadherin causes lethal cardiac abnormalities, and mutations in ID proteins cause human cardiomyopathy. A comprehensive screen for novel mechanisms in failing hearts demonstrated that expression of the lysosomal integral membrane protein 2 (LIMP-2) is increased in cardiac hypertrophy and heart failure in both rat and human myocardium. Complete loss of LIMP-2 in genetically engineered mice did not affect cardiac development; however, these LIMP-2 null mice failed to mount a hypertrophic response to increased blood pressure but developed cardiomyopathy. Disturbed cadherin localization in these hearts suggested that LIMP-2 has important functions outside lysosomes. Indeed, we also find LIMP-2 in the ID, where it associates with cadherin. RNAi-mediated knockdown of LIMP-2 decreases the binding of phosphorylated β-catenin to cadherin, whereas overexpression of LIMP-2 has the opposite effect. Collectively, our data show that LIMP-2 is crucial to mount the adaptive hypertrophic response to cardiac loading. We demonstrate a novel role for LIMP-2 as an important mediator of the ID.
Erscheinungsjahr
2007
Zeitschriftentitel
Journal of Experimental Medicine
Band
204
Ausgabe
5
Seite(n)
1227-1235
ISSN
0022-1007
eISSN
1540-9538
Page URI
https://pub.uni-bielefeld.de/record/2953353

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Schroen B, Leenders JJ, van Erk A, et al. Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy. Journal of Experimental Medicine. 2007;204(5):1227-1235.
Schroen, B., Leenders, J. J., van Erk, A., Bertrand, A. T., van Loon, M., van Leeuwen, R. E., Kubben, N., et al. (2007). Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy. Journal of Experimental Medicine, 204(5), 1227-1235. https://doi.org/10.1084/jem.20070145
Schroen, B., Leenders, J. J., van Erk, A., Bertrand, A. T., van Loon, M., van Leeuwen, R. E., Kubben, N., Duisters, R. F., Schellings, M. W., Janssen, B. J., et al. (2007). Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy. Journal of Experimental Medicine 204, 1227-1235.
Schroen, B., et al., 2007. Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy. Journal of Experimental Medicine, 204(5), p 1227-1235.
B. Schroen, et al., “Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy”, Journal of Experimental Medicine, vol. 204, 2007, pp. 1227-1235.
Schroen, B., Leenders, J.J., van Erk, A., Bertrand, A.T., van Loon, M., van Leeuwen, R.E., Kubben, N., Duisters, R.F., Schellings, M.W., Janssen, B.J., Debets, J.J., Schwake, M., Høydal, M.A., Heymans, S., Saftig, P., Pinto, Y.M.: Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy. Journal of Experimental Medicine. 204, 1227-1235 (2007).
Schroen, Blanche, Leenders, Joost J., van Erk, Arie, Bertrand, Anne T., van Loon, Mirjam, van Leeuwen, Rick E., Kubben, Nard, Duisters, Rudy F., Schellings, Mark W., Janssen, Ben J., Debets, Jacques J., Schwake, Michael, Høydal, Morten A., Heymans, Stephane, Saftig, Paul, and Pinto, Yigal M. “Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy”. Journal of Experimental Medicine 204.5 (2007): 1227-1235.

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