title: CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function.
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.
authors.affiliation: Hubrecht Institute, Developmental Biology and Stem Cell Research, 3584 CT, Utrecht, The Netherlands.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Beqqali
authors.forename: Jantine
authors.initials: J
authors.lastname: Monshouwer-Kloots
authors.forename: Rui
authors.initials: R
authors.lastname: Monteiro
authors.forename: Maaike
authors.initials: M
authors.lastname: Welling
authors.forename: Jeroen
authors.initials: J
authors.lastname: Bakkers
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ehler
authors.forename: Arie
authors.initials: A
authors.lastname: Verkleij
authors.forename: Christine
authors.initials: C
authors.lastname: Mummery
authors.forename: Robert
authors.initials: R
authors.lastname: Passier
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D030801:Animals, Genetically Modified; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004622:Embryo, Mammalian; D055785:Gene Knockdown Techniques; D006321:Heart / Q000196:embryology / Q000502:physiology; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000196:embryology / Q000502:physiology / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D012518:Sarcomeres / Q000378:metabolism* / Q000648:ultrastructure; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008840:Microfilament Proteins; C503979:SYNPO2 protein, human; C551862:SYNPO2L protein, human; C551863:Synpo2l protein, rat; D029961:Zebrafish Proteins; C551864:synpo2la protein, zebrafish