Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China.
Institute for Glyco-core Research (iGCORE), Gifu University, Japan.
FEBS Lett. 2021 Jun;595(11):1542-1558. doi: 10.1002/1873-3468.14083. Epub 2021 Apr 24.
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 targeting via the 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.
哺乳动物基因组中编码了超过 100 种糖基磷脂酰肌醇锚定蛋白（GPI-APs）。这些蛋白质是如何被靶向并易位到内质网（ER）的，目前还不是很清楚。在这里，我们揭示了许多 GPI-APs，如 CD59、CD55 和 CD109，利用人类 SND2（hSND2）依赖性 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-APs 靶向 ER。GPI-APs 的 N 端信号序列和 C 端 GPI 附着信号都通过 hSND2 依赖性途径有助于 ER 靶向。特别是，C 端 GPI 附着信号的疏水性是 hSND2 依赖性的决定因素。我们的研究结果解释了 GPI-APs 在哺乳动物细胞中 ER 靶向的途径和机制。
