PUBLICATION

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

Authors
Beqqali, A., Monshouwer-Kloots, J., Monteiro, R., Welling, M., Bakkers, J., Ehler, E., Verkleij, A., Mummery, C., and Passier, R.
ID
ZDB-PUB-100317-14
Date
2010
Source
Journal of Cell Science   123(Pt 7): 1141-1150 (Journal)
Registered Authors
Bakkers, Jeroen
Keywords
CHAP, Synpo2l, Z-disc, Heart development, Muscle, Sarcomere
MeSH Terms
  • Active Transport, Cell Nucleus
  • Animals
  • Animals, Genetically Modified
  • COS Cells
  • Cell Nucleus/metabolism*
  • Chlorocebus aethiops
  • Embryo, Mammalian
  • Gene Knockdown Techniques
  • Heart/embryology
  • Heart/physiology
  • Mice
  • Microfilament Proteins/genetics
  • Microfilament Proteins/metabolism*
  • Muscle Development
  • Muscle, Skeletal/embryology
  • Muscle, Skeletal/physiology
  • Muscle, Skeletal/ultrastructure
  • Myocytes, Cardiac/metabolism*
  • Myocytes, Cardiac/ultrastructure
  • Rats
  • Sarcomeres/metabolism*
  • Sarcomeres/ultrastructure
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
20215401 Full text @ J. Cell Sci.
Abstract
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.
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