ABCA5 resides in lysosomes, and ABCA5 knockout mice develop lysosomal disease-like symptoms
ABCA5 resides in lysosomes, and ABCA5 knockout mice develop lysosomal disease-like symptoms
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DOI：
10.1128/mcb.25.10.4138-4149.2005
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发表时间：
2005-05-01
影响因子：
5.3
通讯作者：
Yamaguchi, A
中科院分区：
文献类型：
--
作者：
Kubo, Y;Sekiya, S;Yamaguchi, A
ABCA 5是ABC转运蛋白A亚家族的成员，并且通过逆转录-PCR鉴定了新生小鼠脑和神经细胞中的小鼠直向同源物（mABCA 5）。全长cDNA克隆显示mABCA 5由1，642个氨基酸残基组成，并且其推定结构是具有两组六个跨膜区段和一个核苷酸结合结构域的完整型ABC转运蛋白。免疫组织化学研究显示mABCA 5在脑、肺、心脏和甲状腺中表达。亚细胞定位分析表明，mABCA 5是溶酶体和晚期内体的居民。Abca 5（-/-）小鼠表现出与心脏中的几种溶酶体疾病相似的症状，尽管在脑或肺中未发现显著异常。他们在成年后出现了扩张的心肌病样心脏，并因心血管系统抑郁而死亡。此外，Abca 5（-/-）小鼠还表现出眼球突出和甲状腺塌陷。因此，ABCA 5是一种与溶酶体疾病相关的蛋白质，并发挥重要作用，特别是在心肌细胞和滤泡细胞中。
ABCA5 is a member of the ABC transporter A subfamily, and a mouse orthologue (mABCA5) in newborn mouse brain and neural cells was identified by reverse transcription-PCR. Full-length cDNA cloning revealed that mABCA5 consists of 1,642 amino acid residues and that its putative structure is that of a full-type ABC transporter having two sets of six transmembrane segments and a nucleotide binding domain. Immunohistochemical studies revealed that mABCA5 is expressed in brain, lung, heart, and thyroid gland. A subcellular localization analysis showed that mABCA5 is a resident of lysosomes and late endosomes. Abca5(-/-) mice exhibited symptoms similar to those of several lysosomal diseases in heart, although no prominent abnormalities were found in brain or lung. They developed a dilated cardiomyopathy-like heart after reaching adulthood and died due to depression of the cardiovascular system. In addition, Abca5(-/-) mice also exhibited exophthalmos and collapse of the thyroid gland. Therefore, ABCA5 is a protein related to a lysosomal disease and plays important roles, especially in cardiomyocytes and follicullar cells.