Zastrow Michael S, Vlcek Sylvia, Wilson Katherine L
Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
J Cell Sci. 2004 Mar 1;117(Pt 7):979-87. doi: 10.1242/jcs.01102.
What do such diverse molecules as DNA, actin, retinoblastoma protein and protein kinase Calpha all have in common? They and additional partners bind 'A-type' lamins, which form stable filaments in animal cell nuclei. Mutations in A-type lamins cause a bewildering range of tissue-specific diseases, termed 'laminopathies', including Emery-Dreifuss muscular dystrophy and the devastating Hutchinson-Gilford progeria syndrome, which mimics premature aging. Considered individually and collectively, partners for A-type lamins form four loose groups: architectural partners, chromatin partners, gene-regulatory partners and signaling partners. We describe 16 partners in detail, summarize their binding sites in A-type lamins, and sketch portraits of ternary complexes and functional pathways that might depend on lamins in vivo. On the basis of our limited current knowledge, we propose lamin-associated complexes with multiple components relevant to nuclear structure (e.g. emerin, nesprin 1alpha, actin) or signaling and gene regulation (e.g. LAP2alpha, retinoblastoma, E2F-DP heterodimers, genes) as 'food for thought'. Testing these ideas will deepen our understanding of nuclear function and human disease.
诸如DNA、肌动蛋白、视网膜母细胞瘤蛋白和蛋白激酶Cα等如此多样的分子有什么共同之处呢？它们以及其他一些分子伴侣会与“A型”核纤层蛋白结合，这些核纤层蛋白在动物细胞核中形成稳定的细丝。A型核纤层蛋白的突变会引发一系列令人困惑的组织特异性疾病，即“核纤层蛋白病”，包括埃默里 - 德赖富斯肌营养不良症以及模拟早衰的严重哈钦森 - 吉尔福德早衰综合征。单独来看以及综合起来看，A型核纤层蛋白的分子伴侣形成了四个松散的类别：结构分子伴侣、染色质分子伴侣、基因调控分子伴侣和信号传导分子伴侣。我们详细描述了16种分子伴侣，总结了它们在A型核纤层蛋白中的结合位点，并勾勒了可能在体内依赖于核纤层蛋白的三元复合物和功能途径的概况。基于我们目前有限的知识，我们提出将与核结构（如emerin、nesprin 1α、肌动蛋白）或信号传导及基因调控（如LAP2α、视网膜母细胞瘤、E2F - DP异二聚体、基因）相关的多种成分的核纤层蛋白相关复合物作为“思考方向”。对这些观点进行验证将加深我们对核功能和人类疾病的理解。
