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  Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy

Peche, V. S., Holak, T. A., Burgute, B. D., Kosmas, K., Kale, S. P., Wunderlich, F. T., et al. (2013). Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy. CELLULAR AND MOLECULAR LIFE SCIENCES, 70(3), 527-543. doi:10.1007/s00018-012-1142-y.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-AC26-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-AC27-C
Genre: Journal Article

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 Creators:
Peche, Vivek S.1, Author
Holak, Tad A.2, Author              
Burgute, Bhagyashri D.1, Author
Kosmas, Kosmas1, Author
Kale, Sushant P.1, Author
Wunderlich, F. Thomas1, Author
Elhamine, Fatiha1, Author
Stehle, Robert1, Author
Pfitzer, Gabriele1, Author
Nohroudi, Klaus1, Author
Addicks, Klaus1, Author
Stoeckigt, Florian1, Author
Schrickel, Jan W.1, Author
Gallinger, Julia1, Author
Schleicher, Michael3, Author              
Noegel, Angelika A.1, Author
Affiliations:
1external, ou_persistent22              
2Holak, Tad / NMR Spectroscopy, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565154              
3External Organizations, ou_persistent22              

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Free keywords: VENTRICULAR DILATED CARDIOMYOPATHY; CONGESTIVE-HEART-FAILURE; ISCHEMIA/REPERFUSION INJURY; ACTIN DYNAMICS; DEFICIENT MICE; APOPTOSIS; EXPRESSION; ESTROGEN; FEMALE; MOUSEM-line; Filament assembly; WH2 domain; Cardiomyopathy;
 Abstract: Cyclase-associated proteins are highly conserved proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium-regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2's role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physiological functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects.

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Language(s): eng - English
 Dates: 2013-02
 Publication Status: Published in print
 Pages: 17
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: ISI: 000313363600009
DOI: 10.1007/s00018-012-1142-y
 Degree: -

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Title: CELLULAR AND MOLECULAR LIFE SCIENCES
Source Genre: Journal
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Publ. Info: PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND : SPRINGER BASEL AG
Pages: - Volume / Issue: 70 (3) Sequence Number: - Start / End Page: 527 - 543 Identifier: ISSN: 1420-682X