CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function
CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function
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DOI：
10.1242/jcs.063859
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发表时间：
2010-04-01
影响因子：
4
通讯作者：
Passier, Robert
中科院分区：
文献类型：
--
作者：
Beqqali, Abdelaziz;Monshouwer-Kloots, Jantine;Passier, Robert
近年来，对Z盘功能的认识已经从允许力传递的肌丝的被动锚改变为能够感知和转导细胞外信号的动态多复合体结构。在这里，我们描述了一个新的Z盘蛋白，我们命名为cytoskeleton心脏富集肌动蛋白相关蛋白（cytoskeleton heart-enriched actin-associated protein），在体外和体内分化的心脏和骨骼肌中表达。有趣的是，除了它的肌节定位外，它还能够移位到细胞核。当在体外异位表达时，cardiac与细胞质和细胞核中的丝状肌动蛋白相关，但在大鼠新生心肌细胞中，cardiac破坏了另一种Z盘蛋白α-辅肌动蛋白的亚细胞定位。更重要的是，在斑马鱼中敲低BMP 3基因会导致异常的心脏和骨骼肌发育和功能。这些发现表明，肌节是肌节的重要组成部分，在肌肉发育中起重要作用。
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.