Aciculin interacts with filamin C and Xin and is essential for myofibril assembly, remodeling and maintenance
Aciculin interacts with filamin C and Xin and is essential for myofibril assembly, remodeling and maintenance
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DOI：
10.1242/jcs.152157
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发表时间：
2014-08-15
影响因子：
4
通讯作者：
Fuerst, Dieter O.
中科院分区：
文献类型：
--
作者：
Molt, Sibylle;Buehrdel, John B.;Fuerst, Dieter O.
细丝蛋白C(FlnC)和肌动蛋白结合重复序列蛋白(XIRPs)是主要在心肌和骨骼肌中表达的多接头蛋白，在肌原纤维的组装、修复及其在膜上的附着过程中起着重要作用。我们鉴定了抗肌营养不良蛋白结合蛋白针状蛋白(又称磷酸葡萄糖变位酶样蛋白5，PGM5)是FlnC和Xin的一个新的相互作用伙伴。这三种蛋白均共同定位于心肌的间盘和骨骼肌的肌腱连接处，而FlnC和Accuin也共同定位于成熟的Z盘中。在培养的哺乳动物骨骼肌细胞中进行的双分子荧光互补实验表明，Xin和Accuin也在含有FlnC的未成熟肌纤维以及电脉冲刺激(EPS)诱导的肌纤维重塑和修复区域相互作用。光漂白后荧光恢复(FRAP)实验表明，针叶蛋白是一种高度动态和可移动的蛋白质。肌管中的针状蛋白被敲除导致肌原纤维的组装、排列和膜附着失败，肌原纤维数量大量减少。在斑马鱼胚胎中发现了一个高度相似的表型，即缺乏针叶蛋白。我们的结果指出，到目前为止还没有被认识的，但必不可少的，在肌原纤维的形成、维持和重塑中的作用。
Filamin C (FLNc) and Xin actin-binding repeat-containing proteins (XIRPs) are multi-adaptor proteins that are mainly expressed in cardiac and skeletal muscles and which play important roles in the assembly and repair of myofibrils and their attachment to the membrane. We identified the dystrophin-binding protein aciculin (also known as phosphoglucomutase-like protein 5, PGM5) as a new interaction partner of FLNc and Xin. All three proteins colocalized at intercalated discs of cardiac muscle and myotendinous junctions of skeletal muscle, whereas FLNc and aciculin also colocalized in mature Z-discs. Bimolecular fluorescence complementation experiments in developing cultured mammalian skeletal muscle cells demonstrated that Xin and aciculin also interact in FLNc-containing immature myofibrils and areas of myofibrillar remodeling and repair induced by electrical pulse stimulation (EPS). Fluorescence recovery after photobleaching (FRAP) experiments showed that aciculin is a highly dynamic and mobile protein. Aciculin knockdown in myotubes led to failure in myofibril assembly, alignment and membrane attachment, and a massive reduction in myofibril number. A highly similar phenotype was found upon depletion of aciculin in zebrafish embryos. Our results point to a thus far unappreciated, but essential, function of aciculin in myofibril formation, maintenance and remodeling.