Molecular tag for promoting N-glycan maturation in the cargo receptor-mediated secretion pathway

被引：0

作者：

Yagi, Hirokazu ^{[1
,2
]}

Yamada, Rino ^{[1
]}

Saito, Taiki ^{[1
,2
,3
]}

Honda, Rena ^{[1
,3
,4
]}

Nakano, Rio ^{[1
]}

Inutsuka, Kengo ^{[1
]}

Tateo, Seigo ^{[1
,2
,3
]}

Kusano, Hideo ^{[5
]}

Nishimura, Kumiko ^{[5
]}

Yanaka, Saeko ^{[1
,2
,3
,4
]}

Tojima, Takuro ^{[6
]}

Nakano, Akihiko ^{[6
]}

Furukawa, Jun-ichi ^{[7
]}

Yagi-Utsumi, Maho ^{[1
,2
,3
,4
]}

Adachi, Shungo ^{[5
]}

Kato, Koichi ^{[1
,2
,3
,4
]}

机构：

[1] Nagoya City Univ, Fac & Grad Sch Pharmaceut Sci, Nagoya 4678603, Japan

[2] Exploratory Res Ctr Life & Living Syst ExCELLS, Okazaki 4448787, Japan

[3] Natl Inst Nat Sci, Inst Mol Sci, Okazaki 4448787, Japan

[4] SOKENDAI, Grad Univ Adv Studies, Okazaki 4448787, Japan

[5] Natl Canc Ctr, Dept Prote, Tokyo 1040045, Japan

[6] RIKEN, Ctr Adv Photon, Wako, Saitama 3510198, Japan

[7] Nagoya Univ, Inst Glyco Core Res iGCORE, Nagoya 4648601, Japan

来源：

ISCIENCE | 2024年 / 27卷 / 12期

关键词：

FACTOR-VIII; TRANSPORT RECEPTOR; QUALITY-CONTROL; SIALIC-ACID; FACTOR-V; PROTEIN; GOLGI; GLYCOMICS; ERGIC-53; CALNUC;

D O I：

10.1016/j.isci.2024.111457

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 N-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.

引用

页数：14

共 32 条

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