Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome
Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome
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DOI：
10.3858/emm.2009.41.6.043
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发表时间：
2009-06-30
影响因子：
12.8
通讯作者：
Yoon, Sungjoo Kim
中科院分区：
文献类型：
--
作者：
Cho, A-Ri;Yang, Keum-Jin;Yoon, Sungjoo Kim
AAA综合征是一种罕见的遗传性疾病，由失弛缓症-失弛缓症-失弛缓症综合征(AAAS)基因突变引起，该基因编码一种含有色氨酸、天冬氨酸(WD)重复序列的蛋白，称为失弛缓症-失弛缓症-肾上腺功能不全神经性疾病(阿拉丁)。Northern印迹分析表明，2.1kb的AAAS基因在不同组织中均有表达，其中以睾丸和胰腺表达最强。我们发现人类Aladin是一种表观分子量为60 kDa的蛋白质，在肾上腺、脑下垂体和胰腺中表达。此外，使用抗阿拉丁抗体的生化分析支持了先前发现的阿拉丁在核膜中的定位。突变S544G和S544X表明，S544残基的改变影响了阿拉丁对核膜的正确靶向。
Triple A syndrome is a rare genetic disorder caused by mutations in the achalasia-addisonianism-alacrima syndrome (AAAS) gene which encodes a tryptophan aspartic acid (WD) repeat-containing protein named alacrima-achalasia-adrenal insufficiency neurologic disorder (ALADIN). Northern blot analysis shows that the 2.1 kb AAAS mRNA is expressed in various tissues with stronger expression in testis and pancreas. We show that human ALADIN is a protein with an apparent molecular weight of 60 kDa, and expressed in the adrenal gland, pituitary gland and pancreas. Furthermore, biochemical analysis using anti-ALADIN antibody supports the previous finding of the localization of ALADIN in the nuclear membrane. The mutations S544G and S544X show that alteration of S544 residue affects correct targeting of ALADIN to the nuclear membrane.