Trafficking defect of mutant kidney anion exchanger 1 (kAE1) proteins associated with distal renal tubular acidosis and Southeast Asian ovalocytosis

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• 作者：Nunghathai Sawasdee ; Wandee Udomchaiprasertkul ; Sansanee Noisakran ; Nanyawan Rungroj ; Varaporn Akkarapatumwong and Pa-thai Yenchitsomanus
• 关键词：Distal renal tubular acidosis (dRTA) ; Kidney anion exchanger 1 (kAE1) ; Southeast Asian ovalocytosis (SAO) ; Compound heterozygous mutation ; Trafficking defect ; Epitope tag ; Green fluorescent protein (GFP) ; Thai
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2006
• 出版时间：24 November 2006
• 年：2006
• 卷：350
• 期：3
• 页码：723-730
• 全文大小：797 K

文摘

Compound heterozygous anion exchanger 1 (AE1) SAO/G701D mutations result in distal renal tubular acidosis with Southeast Asian ovalocytosis. Interaction, trafficking and localization of wild-type and mutant (SAO and G701D) kAE1 proteins fused with hemagglutinin, six-histidine, Myc, or green fluorescence protein (GFP) were examined in human embryonic kidney (HEK) 293 cells. When individually expressed, wild-type kAE1 was localized at cell surface while mutant kAE1 SAO and G701D were intracellularly retained. When co-expressed, wild-type kAE1 could form heterodimer with kAE1 SAO or kAE1 G701D and could rescue mutant kAE1 proteins to express on the cell surface. Co-expression of kAE1 SAO and kAE1 G701D also resulted in heterodimer formation but intracellular retention without cell surface expression, suggesting their trafficking defect and failure to rescue each other to the plasma membrane, most likely the molecular mechanism of the disease in the compound heterozygous condition.