Gregorio Carol C, Perry Cynthia N, McElhinny Abigail S
Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA.
J Muscle Res Cell Motil. 2005;26(6-8):389-400. doi: 10.1007/s10974-005-9021-x.
The efficient functioning of striated muscle is dependent upon the proper alignment and coordinated activities of several cytoskeletal networks including myofibrils, microtubules, and intermediate filaments. However, the exact molecular mechanisms dictating their cooperation and contributions during muscle differentiation and maintenance remain unknown. Recently, the muscle specific RING finger (MURF) family members have established themselves as excellent candidates for linking myofibril components (including the giant, multi-functional protein, titin/connectin), with microtubules, intermediate filaments, and nuclear factors. MURF-1, the only family member expressed throughout development, has been implicated in several studies as an ubiquitin ligase that is upregulated in response to multiple stimuli during muscle atrophy. Cell culture studies suggest that MURF-1 specifically has a role in maintaining titin M-line integrity and yeast two-hybrid studies point toward its participation in muscle stress response pathways and gene expression. MURF-2 is developmentally down-regulated and is assembled at the M-line region of the sarcomere and with microtubules. Functionally, its expression is critical for maintenance of the sarcomeric M-line region, specific populations of stable microtubules, desmin and vimentin intermediate filaments, as well as for myoblast fusion and differentiation. A recent study also links MURF-2 to a titin kinase-based protein complex that is reportedly activated upon mechanical signaling. Finally, MURF-3 is developmentally upregulated, associates with microtubules, the sarcomeric M-line (this report) and Z-line, and is required for microtubule stability and myogenesis. Here, we focus on the biochemical and functional properties of this intriguing family of muscle proteins, and discuss how they may tie together titin-mediated myofibril signaling pathways (perhaps involving the titin kinase domain), biomechanical signaling, the muscle stress response, and gene expression.
横纹肌的高效运作依赖于几种细胞骨架网络的正确排列和协同活动，这些网络包括肌原纤维、微管和中间丝。然而，在肌肉分化和维持过程中决定它们协同作用及贡献的精确分子机制仍不清楚。最近，肌肉特异性环指（MURF）家族成员已成为连接肌原纤维成分（包括巨大的多功能蛋白肌联蛋白/伴肌动蛋白）与微管、中间丝和核因子的优秀候选者。MURF-1是在整个发育过程中表达的唯一家族成员，在多项研究中被认为是一种泛素连接酶，在肌肉萎缩期间对多种刺激作出反应时上调。细胞培养研究表明，MURF-1特别在维持肌联蛋白M线完整性方面发挥作用，酵母双杂交研究表明它参与肌肉应激反应途径和基因表达。MURF-2在发育过程中表达下调，在肌节的M线区域以及与微管组装在一起。在功能上，其表达对于维持肌节M线区域、特定群体的稳定微管、结蛋白和波形蛋白中间丝以及成肌细胞融合和分化至关重要。最近一项研究还将MURF-2与一种据报道在机械信号作用下被激活的基于肌联蛋白激酶的蛋白复合物联系起来。最后，MURF-3在发育过程中上调，与微管、肌节M线（本报告）和Z线相关联，是微管稳定性和成肌所必需的。在这里，我们重点关注这个有趣的肌肉蛋白家族的生化和功能特性，并讨论它们如何将肌联蛋白介导的肌原纤维信号通路（可能涉及肌联蛋白激酶结构域）、生物力学信号、肌肉应激反应和基因表达联系在一起。
