Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence.
Topological regulation of a transmembrane protein by luminal-to-cytosolic retrotranslocation of glycosylated sequence.
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DOI：
10.1016/j.celrep.2023.112311
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发表时间：
2023-04-25
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
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跨膜蛋白必须采用适当的拓扑结构才能发挥其功能。我们之前已经证明神经酰胺通过改变跨膜蛋白的拓扑结构来调节TM4SF20（跨膜4 L6家族20），但其潜在的机制仍然不清楚。在这里，我们报道TM4SF20在内质网（ER）中合成，具有细胞质C端和最后一个跨膜螺旋之前的管腔环，其中N132， N148和N163被糖基化。在缺乏神经酰胺的情况下，糖基化N163周围的序列（而不是N132）从管腔逆转录到细胞质中，而不依赖于内质酰胺相关的降解。伴随这种逆转录，蛋白质的C端从细胞质转移到管腔。神经酰胺延缓逆转录过程，导致最初合成的蛋白质积累。我们的研究结果表明，n -链聚糖虽然在管腔中合成，但可能通过逆转录易位暴露于细胞质，这一反应可能在跨膜蛋白的拓扑调节中起关键作用。Wang等人发现，n -链聚糖虽然在内质网腔中合成，但通过反转录易位暴露于细胞质中。他们表明，神经酰胺介导的跨膜蛋白TM4SF20拓扑结构的改变需要逆转录。
Transmembrane proteins must adopt proper topology to perform their functions. We previously demonstrated that ceramide regulates TM4SF20 (transmembrane 4 L6 family 20) by altering the topology of the transmembrane protein, but the underlying mechanism remains obscure. Here we report that TM4SF20 is synthesized in the endoplasmic reticulum (ER) with a cytosolic C terminus and a luminal loop before the last transmembrane helix where N132, N148, and N163 are glycosylated. In the absence of ceramide, the sequence surrounding glycosylated N163 but not N132 is retrotranslocated from lumen to cytosol independent of ER-associated degradation. Accompanying this retrotranslocation, the C terminus of the protein is relocated from cytosol to lumen. Ceramide delays the retrotranslocation process, causing accumulation of the protein that is originally synthesized. Our findings suggest that N-linked glycans, although synthesized in the lumens, may be exposed to cytosol through retrotranslocation, a reaction that may play a crucial role in topological regulation of transmembrane proteins. Wang et al. find that an N-linked glycan, although synthesized in the ER lumen, is exposed to the cytosol through retrotranslocation. They show that retrotranslocation is required for ceramide-mediated alteration of the topology of a transmembrane protein, TM4SF20.
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DOI：
10.1016/j.bbamcr.2011.10.013
发表时间：
2012-03
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
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通讯作者：
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DOI：
10.1016/j.jbc.2021.101415
发表时间：
2021-12
期刊：
The Journal of biological chemistry
影响因子：
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DOI：
10.1126/science.abf9232
发表时间：
2021-09-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bang YJ;Hu Z;Li Y;Gattu S;Ruhn KA;Raj P;Herz J;Hooper LV
通讯作者：
Hooper LV
影响因子：
7.7
作者：
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影响因子：
7.7
作者：
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