TY - JOUR
T1 - CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function
AU - Beqqali, A.
AU - Monshouwer-Kloots, J.
AU - Monteiro, R.
AU - Welling, M.
AU - Bakkers, J.
AU - Ehler, E.
AU - Verkleij, A.J.
AU - Mummery, C.L.
AU - Passier, R.
N1 - Reporting year: 2010
Metis note: jcs.063859 [pii]
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
U2 - 10.1242/jcs.063859
DO - 10.1242/jcs.063859
M3 - Article
SN - 0021-9533
VL - 123
SP - 1141
EP - 1150
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - Pt 7
ER -