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CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function

Beqqali, A. and Monshouwer-Kloots, J. and Monteiro, R. and Welling, M. and Bakkers, J. and Ehler, E. and Verkleij, A.J. and Mummery, C.L. and Passier, R. (2010) CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function. Journal of Cell Science, 123, 1141-50. ISSN 0021-9533.

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In recent years, the perception of Z-disc function has changed from a passive anchor for myofilaments that allows transmission of force, to a dynamic multicomplex structure, capable of sensing and transducing extracellular signals. Here, we describe a new Z-disc protein, which we named CHAP (cytoskeletal heart-enriched actin-associated protein), expressed in differentiating heart and skeletal muscle in vitro and in vivo. Interestingly, in addition to its sarcomeric localization, CHAP was also able to translocate to the nucleus. CHAP was associated with filamentous actin in the cytoplasm and the nucleus when expressed ectopically in vitro, but in rat neonatal cardiomyocytes, CHAP disrupted the subcellular localization of alpha-actinin, another Z-disc protein. More importantly, knockdown of CHAP in zebrafish resulted in aberrant cardiac and skeletal muscle development and function. These findings suggest that CHAP is a critical component of the sarcomere with an important role in muscle development.

Item Type:Article
Institutes:Hubrecht Instituut
ID Code:9474
Deposited On:04 Jan 2011 01:00
Last Modified:07 Sep 2011 17:01

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