Dataset Information

Myozap, a novel intercalated disc protein, activates serum response factor-dependent signaling and is required to maintain cardiac function in vivo.

ABSTRACT:

Rationale

The intercalated disc (ID) is a highly specialized cell-cell contact structure that ensures mechanical and electric coupling of contracting cardiomyocytes. Recently, the ID has been recognized to be a hot spot of cardiac disease, in particular inherited cardiomyopathy.

Objective

Given its complex structure and function we hypothesized that important molecular constituents of the ID still remain unknown.

Methods and results

Using a bioinformatics screen, we discovered and cloned a previously uncharacterized 54 kDa cardiac protein which we termed Myozap (Myocardium-enriched zonula occludens-1-associated protein). Myozap is strongly expressed in the heart and lung. In cardiac tissue it localized to the ID and directly binds to desmoplakin and zonula occludens-1. In a yeast 2-hybrid screen for additional binding partners of Myozap we identified myosin phosphatase-RhoA interacting protein (MRIP), a negative regulator of Rho activity. Myozap, in turn, strongly activates SRF-dependent transcription through its ERM (Ezrin/radixin/moesin)-like domain in a Rho-dependent fashion. Finally, in vivo knockdown of the Myozap ortholog in zebrafish led to severe contractile dysfunction and cardiomyopathy.

Conclusions

Taken together, these findings reveal Myozap as a previously unrecognized component of a Rho-dependent signaling pathway that links the intercalated disc to cardiac gene regulation. Moreover, its subcellular localization and the observation of a severe cardiac phenotype in zebrafish, implicate Myozap in the pathogenesis of cardiomyopathy.

SUBMITTER: Seeger TS

PROVIDER: S-EPMC2856095 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Publications

Myozap, a novel intercalated disc protein, activates serum response factor-dependent signaling and is required to maintain cardiac function in vivo.

Seeger Thalia S TS Frank Derk D Rohr Claudia C Will Rainer R Just Steffen S Grund Christine C Lyon Robert R Luedde Mark M Koegl Manfred M Sheikh Farah F Rottbauer Wolfgang W Franke Werner W WW Katus Hugo A HA Olson Eric N EN Frey Norbert N

Circulation research 20100121 5

<h4>Rationale</h4>The intercalated disc (ID) is a highly specialized cell-cell contact structure that ensures mechanical and electric coupling of contracting cardiomyocytes. Recently, the ID has been recognized to be a hot spot of cardiac disease, in particular inherited cardiomyopathy.<h4>Objective</h4>Given its complex structure and function we hypothesized that important molecular constituents of the ID still remain unknown.<h4>Methods and results</h4>Using a bioinformatics screen, we discove ...[more]

PMID: 20093627

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Dataset Information

Myozap, a novel intercalated disc protein, activates serum response factor-dependent signaling and is required to maintain cardiac function in vivo.

Rationale

Objective

Methods and results

Conclusions

Publications

Myozap, a novel intercalated disc protein, activates serum response factor-dependent signaling and is required to maintain cardiac function in vivo.

Similar Datasets

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