Characterization of the complex of the lysosomal membrane transporter MFSD1 and its accessory subunit GLMP

Characterization of the complex of the lysosomal membrane transporter MFSD1 and its accessory subunit GLMP
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溶酶体膜转运蛋白 MFSD1 及其辅助亚基 GLMP 复合物的表征

DOI:
10.1096/fj.202000912rr
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发表时间:
2020
期刊:
The FASEB Journal
影响因子:
--
通讯作者:
M. Damme
M. Damme
中科院分区:
--
文献类型:
--
作者:
Massa Lopez;L. Kahlau;K. E. J. Jungnickel;C. Low;M. Damme

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两种溶酶体整合膜蛋白MFSD 1和GLMP形成紧密复合物,其赋予两种相互作用伴侣对溶酶体蛋白水解的保护。我们在这里完善了两种蛋白质的分子相互作用,发现GLMP的管腔结构域单独,而不是其跨膜结构域或其短胞质尾,传达保护和介导与MFSD 1的相互作用。我们的数据支持的发现,相互作用是必不可少的复杂的稳定。这些结果得到了以下观察结果的补充:GLMP的N-糖基化一般对保护至关重要,但N-聚糖类型(高甘露糖型或复合型)或单个N-聚糖链并非如此。我们观察到,这两种蛋白质的相互作用已经开始在内质网,并定量地依赖于对方。这两种蛋白质可以影响,反之亦然,它们的细胞内运输到溶酶体除了保护免受蛋白水解。最后,我们提供的证据表明,MFSD 1可以在体外和体内形成同源二聚体。我们的数据完善了复杂的相互作用之间的亲密夫妇的溶酶体转运蛋白和它的辅助亚基。
The two lysosomal integral membrane proteins MFSD1 and GLMP form a tight complex that confers protection of both interaction partners against lysosomal proteolysis. We here refined the molecular interaction of the two proteins and found that the luminal domain of GLMP alone, but not its transmembrane domain or its short cytosolic tail, conveys protection and mediates the interaction with MFSD1. Our data support the finding that the interaction is essential for the stabilization of the complex. These results are complemented by the observation that N‐glycosylation of GLMP in general, but not the type of N‐glycans (high‐mannose‐type or complex‐type) or individual N‐glycan chains, are essential for protection. We observed that the interaction of both proteins already starts in the endoplasmic reticulum, and quantitatively depends on each other. Both proteins can affect vice versa their intracellular trafficking to lysosomes in addition to the protection from proteolysis. Finally, we provide evidence that MFSD1 can form homodimers both in vitro and in vivo. Our data refine the complex interplay between an intimate couple of a lysosomal transporter and its accessory subunit.
生物合成、糖基化、通过高尔基体系统的运动,以及通过三种溶酶体整合膜蛋白的 N 连接碳水化合物独立机制转运到溶酶体。
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