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Abstract：
Plectin, a high-molecular-weight cytoskeletal linker protein, binds with high affinity to intermediate filaments of all types and connects them to junctional complexes, organelles, and inner membrane systems. In addition, it interacts with actomyosin structures and microtubules. As a multifunctional protein, plectin has been implicated in several multisystemic diseases, the most common of which is epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). A great part of our knowledge about plectin\'s functional diversity has been gained through the analysis of a unique collection of transgenic mice that includes a full (null) knockout (KO), several tissue-restricted and isoform-specific KOs, three double KOs, and two knock-in lines. The key molecular features and pathological phenotypes of these mice will be discussed in this review. In summary, the analysis of the different genetic models indicated that a functional plectin is required for the proper function of striated and simple epithelia, cardiac and skeletal muscle, the neuromuscular junction, and the vascular endothelium, recapitulating the symptoms of humans carrying plectin mutations. The plectin-null line showed severe skin and muscle phenotypes reflecting the importance of plectin for hemidesmosome and sarcomere integrity; whereas the ablation of individual isoforms caused a specific phenotype in myofibers, basal keratinocytes, or neurons. Tissue-restricted ablation of plectin rendered the targeted cells less resilient to mechanical stress. Studies based on animal models other than the mouse, such as zebrafish and C. elegans, will be discussed as well.
摘要：
果胶,一种高分子量的细胞骨架连接蛋白，以高亲和力结合所有类型的中间纤丝，并将它们连接到连接复合物，细胞器,和内膜系统。此外,它与肌动球蛋白结构和微管相互作用。作为一种多功能蛋白质,plectin与几种多系统疾病有关，其中最常见的是单纯性大疱性表皮松解性肌营养不良（EBS-MD）。通过分析一组独特的转基因小鼠，包括全（空）敲除（KO），获得了关于plectin的功能多样性的大部分知识，几种组织限制性和同工型特异性KO，三个双KO,和两条敲门声。本文将讨论这些小鼠的关键分子特征和病理表型。总之,对不同遗传模型的分析表明，条纹和简单上皮的正常功能需要功能性的plectin，心肌和骨骼肌，神经肌肉接头，血管内皮，概述携带plectin突变的人类的症状。plectin-null系显示出严重的皮肤和肌肉表型，反映了plectin对半结膜和肌节完整性的重要性；而单个同工型的消融在肌纤维中引起了特定的表型，基底角质形成细胞，或神经元。PLCIN的组织限制性消融使靶细胞对机械应力的弹性降低。基于小鼠以外的动物模型的研究，比如斑马鱼和秀丽隐杆线虫,也将讨论。
