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

Autor:	Yagi H; 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., Yamada R; Faculty and Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan., Saito T; 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.; Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki 444-8787, Japan., Honda R; Faculty and Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.; Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.; The Graduate University for Advanced Studies, SOKENDAI, Okazaki 444-8787, Japan., Nakano R; Faculty and Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan., Inutsuka K; Faculty and Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan., Tateo S; 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.; Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki 444-8787, Japan., Kusano H; Department of Proteomics, National Cancer Center Research Institute, Tokyo 104-0045 Japan., Nishimura K; Department of Proteomics, National Cancer Center Research Institute, Tokyo 104-0045 Japan., Yanaka S; 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.; Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.; The Graduate University for Advanced Studies, SOKENDAI, Okazaki 444-8787, Japan., Tojima T; RIKEN Center for Advanced Photonics, Wako, Saitama 351-0198, Japan., Nakano A; RIKEN Center for Advanced Photonics, Wako, Saitama 351-0198, Japan., Furukawa JI; Institute for Glyco-core Research (iGCORE), Nagoya University, Nagoya 464-8601, Japan., Yagi-Utsumi M; 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.; Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.; The Graduate University for Advanced Studies, SOKENDAI, Okazaki 444-8787, Japan., Adachi S; Department of Proteomics, National Cancer Center Research Institute, Tokyo 104-0045 Japan., Kato K; 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.; Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.; The Graduate University for Advanced Studies, SOKENDAI, Okazaki 444-8787, Japan.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 Nov 22; Vol. 27 (12), pp. 111457. Date of Electronic Publication: 2024 Nov 22 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.111457
Abstrakt:	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. Competing Interests: The authors declare no competing interests. (© 2024 The Authors.)
Databáze:	MEDLINE
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