Yagi Hirokazu, Yamada Rino, Saito Taiki, Honda Rena, Nakano Rio, Inutsuka Kengo, Tateo Seigo, Kusano Hideo, Nishimura Kumiko, Yanaka Saeko, Tojima Takuro, Nakano Akihiko, Furukawa Jun-Ichi, Yagi-Utsumi Maho, Adachi Shungo, Kato Koichi
Faculty and Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
Exploratory Research Center on Life and Living Systems (ExCELLS), Okazaki 444-8787, Japan.
iScience. 2024 Nov 22;27(12):111457. doi: 10.1016/j.isci.2024.111457. eCollection 2024 Dec 20.
MCFD2 and ERGIC-53 form a cargo receptor complex that plays a crucial role in transporting specific glycoproteins, including blood coagulation factor VIII, from the endoplasmic reticulum to the Golgi apparatus. We have demonstrated that MCFD2 recognizes a 10-amino-acid sequence in factor VIII, thereby facilitating its efficient transport. Moreover, the secretion of biopharmaceutical recombinant glycoproteins, such as erythropoietin, can be enhanced by tagging them with this sequence, which we have termed the "passport sequence" (PS). Here, we found that the PS promotes the galactosylation and sialylation of -glycans on glycoproteins. Furthermore, we discovered that glycoproteins tagged with the PS follow a unique route in the Golgi, where they encounter NUCB1. NUCB1 also recognizes the PS and mediates its interaction with the galactosylation enzyme B4GALT1. These findings offer a promising strategy for controlling the glycosylation of recombinant glycoproteins of biopharmaceutical interest.
MCFD2和ERGIC-53形成一种货物受体复合物，该复合物在将包括凝血因子VIII在内的特定糖蛋白从内质网运输到高尔基体的过程中发挥着关键作用。我们已经证明，MCFD2识别因子VIII中的一个10个氨基酸的序列，从而促进其有效运输。此外，通过用我们称为“护照序列”（PS）的这个序列标记生物制药重组糖蛋白，如促红细胞生成素，可以增强它们的分泌。在这里，我们发现PS促进糖蛋白上聚糖的半乳糖基化和唾液酸化。此外，我们发现用PS标记的糖蛋白在高尔基体中遵循一条独特的途径，在那里它们会遇到NUCB1。NUCB1也识别PS并介导其与半乳糖基化酶B4GALT1的相互作用。这些发现为控制具有生物制药意义的重组糖蛋白的糖基化提供了一种有前景的策略。
