Hubrecht Institute, Developmental Biology and Stem Cell Research, 3584 CT, Utrecht, The Netherlands.
J Cell Sci. 2010 Apr 1;123(Pt 7):1141-50. doi: 10.1242/jcs.063859. Epub 2010 Mar 9.
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.
近年来，对 Z 盘功能的认识已经从肌球蛋白丝的被动锚定点转变为一个能够感受和转导细胞外信号的动态多复合物结构。在这里，我们描述了一种新的 Z 盘蛋白，我们将其命名为 CHAP（细胞骨架心脏丰富的肌动蛋白相关蛋白），它在体外和体内分化的心脏和骨骼肌中表达。有趣的是，除了肌节定位外，CHAP 还能够向核内转移。当 CHAP 在体外异位表达时，它与细胞质和核内的丝状肌动蛋白结合，但在大鼠新生心肌细胞中，CHAP 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 CHAP 导致心脏和骨骼肌发育和功能异常。这些发现表明 CHAP 是肌节的关键组成部分，在肌肉发育中具有重要作用。
