Human SND2 mediates ER targeting of GPI-anchored proteins with low hydrophobic GPI attachment signals
Human SND2 mediates ER targeting of GPI-anchored proteins with low hydrophobic GPI attachment signals
复制标题
人 SND2 通过低疏水性 GPI 附着信号介导 ER 靶向 GPI 锚定蛋白
DOI：
10.1002/1873-3468.14083
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发表时间：
2021
期刊：
影响因子：
3.5
通讯作者：
Fujita M
中科院分区：
文献类型：
--
作者：
Yang J;Hirata T;Liu Y. S;Guo X. Y;Gao X. D;Kinoshita T;Fujita M
哺乳动物基因组中编码了100多个糖基磷脂酰肌醇锚定蛋白(GPI-APs)。目前还不清楚这些蛋白是如何被靶向并转移到内质网(ER)的。在这里，我们揭示了许多GPI-AP，如CD59、CD55和CD109，利用人类SND2(HSND2)依赖的ER靶向机制。我们还发现，信号识别颗粒受体似乎与hSND2合作，将GPI-AP靶向内质网。GPI-AP的N端信号序列和C端GPI连接信号均通过hSND2依赖的途径参与内质网靶向。特别是，C-末端GPI连接信号的疏水性作为hSND2依赖性的决定因素。我们的结果解释了GPI-AP在哺乳动物细胞中内质网靶向的途径和机制。
Over 100 glycosylphosphatidylinositol‐anchored proteins (GPI‐APs) are encoded in the mammalian genome. It is not well understood how these proteins are targeted and translocated to the endoplasmic reticulum (ER). Here, we reveal that many GPI‐APs, such as CD59, CD55, and CD109, utilize human SND2 (hSND2)‐dependent ER targeting machinery. We also found that signal recognition particle receptors seem to cooperate with hSND2 to target GPI‐APs to the ER. Both the N‐terminal signal sequence and C‐terminal GPI attachment signal of GPI‐APs contribute to ER targetingviathe hSND2‐dependent pathway. Particularly, the hydrophobicity of the C‐terminal GPI attachment signal acts as the determinant of hSND2 dependency. Our results explain the route and mechanism of the ER targeting of GPI‐APs in mammalian cells.