Mutations in AQP5, Encoding a Water-Channel Protein, Cause Autosomal-Dominant Diffuse Nonepidermolytic Palmoplantar Keratoderma
Mutations in AQP5, Encoding a Water-Channel Protein, Cause Autosomal-Dominant Diffuse Nonepidermolytic Palmoplantar Keratoderma
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DOI：
10.1016/j.ajhg.2013.06.008
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发表时间：
2013-08-08
影响因子：
9.8
通讯作者：
Kelsell, David P.
中科院分区：
文献类型：
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作者：
Blaydon, Diana C.;Lind, Lisbet K.;Kelsell, David P.
常染色体显性的弥漫性非表皮松解性掌跖角化皮病的特点是受累部位在接触水时出现白色海绵状外观。外显子测序后，发现AQP5编码水通道蛋白水通道蛋白5(AQP5)的错义突变。蛋白质结构分析表明，这些AQP5变异体有可能对正常的通道调节产生影响。免疫荧光显示AQP5在正常和病变掌侧表皮颗粒层的细胞膜上均有表达，表明改变后的AQP5蛋白以正常方式运输。在这里，我们证明了AQP5在掌足底表皮中的作用，并认为改变后的AQP5蛋白保持了在细胞膜上形成开放通道和传导水的能力。
Autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma is characterized by the adoption of a white, spongy appearance of affected areas upon exposure to water. After exome sequencing, missense mutations were identified in AQP5, encoding water-channel protein aquaporin-5 (AQP5). Protein-structure analysis indicates that these AQP5 variants have the potential to elicit an effect on normal channel regulation. Immunofluorescence data reveal the presence of AQP5 at the plasma membrane in the stratum granulosum of both normal and affected palmar epidermis, indicating that the altered AQP5 proteins are trafficked in the normal manner. We demonstrate here a role for AQP5 in the palmoplantar epidermis and propose that the altered AQP5 proteins retain the ability to form open channels in the cell membrane and conduct water.