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

Research output: Contribution to journalArticlepeer-review

Authors

  • Abdelaziz Beqqali
  • Jantine Monshouwer-Kloots
  • Maaike Welling
  • Jeroen Bakkers
  • Elisabeth Ehler
  • Arie Verkleij
  • Christine Mummery
  • Robert Passier

Colleges, School and Institutes

External organisations

  • Hubrecht Laboratory KNAW (Netherlands Institute for Developmental Biology)
  • Leiden University Medical Center - LUMC
  • King's College London
  • Utrecht University

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 a-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.

Details

Original languageEnglish
Pages (from-to)1141-1150
Number of pages10
JournalJournal of Cell Science
Volume123
Issue number7
Publication statusPublished - 1 Apr 2010

Keywords

  • CHAP, Heart development, Muscle, Sarcomere, Synpo2l, Z-disc

ASJC Scopus subject areas