A MUTATION IN THE CONSERVED HELIX TERMINATION PEPTIDE OF KERATIN-5 IN HEREDITARY SKIN BLISTERING
A MUTATION IN THE CONSERVED HELIX TERMINATION PEPTIDE OF KERATIN-5 IN HEREDITARY SKIN BLISTERING
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DOI：
10.1038/356244a0
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发表时间：
1992-03-19
期刊：
影响因子：
64.8
通讯作者：
EADY, RAJ
中科院分区：
文献类型：
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作者：
LANE, EB;RUGG, EL;EADY, RAJ
遗传性单纯性大疱性表皮松解症，表皮基底细胞破裂后皮肤出现水泡。临床变化范围从严重丧失行为能力，特别是在儿童早期，到轻度甚至可能没有临床表现。Dowling-Meara单纯大疱性表皮松解症的特征是表皮成簇的水泡和细胞质中的角蛋白结块1；最近的报道描述了角蛋白14的潜在致病突变（参考文献2,3）。在这里，我们描述了由这些细胞表达的另一个角蛋白（K5，与K14共表达）的另一端的“互补”突变，在螺旋末端肽中从Glu变为Gly，通过改变抗体结合检测到，并通过使用聚合酶链反应测序证实。两个保守的螺旋边界肽被预测为纤维组装所必需的，并且对两个互补（I型和II型）角蛋白的需求是绝对的。单纯大疱性表皮松解病表明角蛋白细胞骨架在抵抗压实应力方面的功能，否则会导致细胞溶解。
IN the hereditary blistering condition epidermolysis bullosa simplex, the skin blisters on trauma following rupture of epidermal basal cells. Clinical variations range from severely incapacitating, especially in early childhood, to mild forms that may not even present clinically. Dowling-Meara epidermolysis bullosa simplex is characterized by clusters of epidermal blisters and keratin clumping in the cytoplasm 1; recent reports describe potentially causal mutations in keratin 14 (refs 2, 3). Here we describe a 'complementary' mutation at the other end of the other keratin expressed by these cells (K5, coexpressed with K14), a change from a Glu to a Gly in the helix termination peptide, detected by altered antibody binding and confirmed by sequencing using the polymerase chain reaction. The two conserved helix boundary peptides are predicted to be essential for filament assembly, and the requirement for two complementary (type I and type II) keratins is absolute. Epidermolysis bullosa simplex diseases demonstrate the function of the keratin cytoskeleton in resisting compaction stresses which otherwise lead to cell lysis.