Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1.
Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1.
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DOI：
10.1038/srep30183
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发表时间：
2016-07-26
影响因子：
4.6
通讯作者：
Imanaka T
中科院分区：
文献类型：
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作者：
Kawaguchi K;Okamoto T;Morita M;Imanaka T
我们之前证明 ABCD4 并不定位于过氧化物酶体，而是定位于内质网 (ER)，因为它缺乏过氧化物酶体靶向所需的 NH2 末端亲水区域。最近有报道称 ABCD4 突变导致溶酶体无法释放维生素 B12。类似的表型是由编码溶酶体膜蛋白 LMBD1 的 LMBRD1 突变引起的。这些发现表明 ABCD4 与 LMBD1 相关，从 ER 易位至溶酶体。该报告证明ABCD4与LMBD1相互作用，然后定位到溶酶体，并且这种易位取决于LMBD1的溶酶体靶向能力。此外，内源性 ABCD4 定位于溶酶体和 ER，并且其溶酶体定位受到 LMBRD1 敲除的干扰。据我们所知，这是第一份证明 ABC 转运蛋白的亚细胞定位是由其与衔接蛋白的关联决定的报告。
We previously demonstrated that ABCD4 does not localize to peroxisomes but rather, the endoplasmic reticulum (ER), because it lacks the NH2-terminal hydrophilic region required for peroxisomal targeting. It was recently reported that mutations in ABCD4 result in a failure to release vitamin B12 from lysosomes. A similar phenotype is caused by mutations in LMBRD1, which encodes the lysosomal membrane protein LMBD1. These findings suggested to us that ABCD4 translocated from the ER to lysosomes in association with LMBD1. In this report, it is demonstrated that ABCD4 interacts with LMBD1 and then localizes to lysosomes, and this translocation depends on the lysosomal targeting ability of LMBD1. Furthermore, endogenous ABCD4 was localized to both lysosomes and the ER, and its lysosomal localization was disturbed by knockout of LMBRD1. To the best of our knowledge, this is the first report demonstrating that the subcellular localization of the ABC transporter is determined by its association with an adaptor protein.