Guillard Mailys, Dimopoulou Aikaterini, Fischer Björn, Morava Eva, Lefeber Dirk J, Kornak Uwe, Wevers Ron A
Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Biochim Biophys Acta. 2009 Sep;1792(9):903-14. doi: 10.1016/j.bbadis.2008.12.009. Epub 2009 Jan 8.
Glycosylation of proteins is one of the most important post-translational modifications. Defects in the glycan biosynthesis result in congenital malformation syndromes, also known as congenital disorders of glycosylation (CDG). Based on the iso-electric focusing patterns of plasma transferrin and apolipoprotein C-III a combined defect in N- and O-glycosylation was identified in patients with autosomal recessive cutis laxa type II (ARCL II). Disease-causing mutations were identified in the ATP6V0A2 gene, encoding the a2 subunit of the vacuolar H(+)-ATPase (V-ATPase). The V-ATPases are multi-subunit, ATP-dependent proton pumps located in membranes of cells and organels. In this article, we describe the structure, function and regulation of the V-ATPase and the phenotypes currently known to result from V-ATPase mutations. A clinical overview of cutis laxa syndromes is presented with a focus on ARCL II. Finally, the relationship between ATP6V0A2 mutations, the glycosylation defect and the ARCLII phenotype is discussed.
蛋白质糖基化是最重要的翻译后修饰之一。聚糖生物合成缺陷会导致先天性畸形综合征，也称为先天性糖基化障碍（CDG）。基于血浆转铁蛋白和载脂蛋白C-III的等电聚焦模式，在常染色体隐性遗传II型皮肤松弛症（ARCL II）患者中发现了N-糖基化和O-糖基化的联合缺陷。在编码液泡H(+)-ATP酶（V-ATPase）α2亚基的ATP6V0A2基因中发现了致病突变。V-ATPase是位于细胞和细胞器膜上的多亚基、依赖ATP的质子泵。在本文中，我们描述了V-ATPase的结构、功能和调节以及目前已知的由V-ATPase突变导致的表型。本文对皮肤松弛综合征进行了临床概述，重点是ARCL II。最后，讨论了ATP6V0A2突变、糖基化缺陷与ARCLII表型之间的关系。
