Details

Autor(en) / Beteiligte

• 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
• Pinto, Yigal M

Titel

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

Ist Teil von

• The Journal of experimental medicine, 2007-05, Vol.204 (5), p.1227-1235

Ort / Verlag

United States: The Rockefeller University Press

Erscheinungsjahr

2007

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 beta-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.