Molecular tag for promoting N-glycan maturation in the cargo receptor-mediated secretion pathway
Summary: 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 VI...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-12-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224026841 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846113059760766976 |
|---|---|
| author | Hirokazu Yagi Rino Yamada Taiki Saito Rena Honda Rio Nakano Kengo Inutsuka Seigo Tateo Hideo Kusano Kumiko Nishimura Saeko Yanaka Takuro Tojima Akihiko Nakano Jun-ichi Furukawa Maho Yagi-Utsumi Shungo Adachi Koichi Kato |
| author_facet | Hirokazu Yagi Rino Yamada Taiki Saito Rena Honda Rio Nakano Kengo Inutsuka Seigo Tateo Hideo Kusano Kumiko Nishimura Saeko Yanaka Takuro Tojima Akihiko Nakano Jun-ichi Furukawa Maho Yagi-Utsumi Shungo Adachi Koichi Kato |
| author_sort | Hirokazu Yagi |
| collection | DOAJ |
| description | Summary: 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. |
| format | Article |
| id | doaj-art-484f63fec76246a485b1c364085a07a9 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-484f63fec76246a485b1c364085a07a92024-12-22T05:29:26ZengElsevieriScience2589-00422024-12-012712111457Molecular tag for promoting N-glycan maturation in the cargo receptor-mediated secretion pathwayHirokazu Yagi0Rino Yamada1Taiki Saito2Rena Honda3Rio Nakano4Kengo Inutsuka5Seigo Tateo6Hideo Kusano7Kumiko Nishimura8Saeko Yanaka9Takuro Tojima10Akihiko Nakano11Jun-ichi Furukawa12Maho Yagi-Utsumi13Shungo Adachi14Koichi Kato15Faculty 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; Corresponding authorFaculty and Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanFaculty 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, JapanFaculty 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, JapanFaculty and Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanFaculty and Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanFaculty 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, JapanDepartment of Proteomics, National Cancer Center Research Institute, Tokyo 104-0045 JapanDepartment of Proteomics, National Cancer Center Research Institute, Tokyo 104-0045 JapanFaculty 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, JapanRIKEN Center for Advanced Photonics, Wako, Saitama 351-0198, JapanRIKEN Center for Advanced Photonics, Wako, Saitama 351-0198, JapanInstitute for Glyco-core Research (iGCORE), Nagoya University, Nagoya 464-8601, JapanFaculty 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, JapanDepartment of Proteomics, National Cancer Center Research Institute, Tokyo 104-0045 JapanFaculty 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224026841BiochemistryProteinProperties of biomoleculesGlycobiologyMolecular biology |
| spellingShingle | Hirokazu Yagi Rino Yamada Taiki Saito Rena Honda Rio Nakano Kengo Inutsuka Seigo Tateo Hideo Kusano Kumiko Nishimura Saeko Yanaka Takuro Tojima Akihiko Nakano Jun-ichi Furukawa Maho Yagi-Utsumi Shungo Adachi Koichi Kato Molecular tag for promoting N-glycan maturation in the cargo receptor-mediated secretion pathway iScience Biochemistry Protein Properties of biomolecules Glycobiology Molecular biology |
| title | Molecular tag for promoting N-glycan maturation in the cargo receptor-mediated secretion pathway |
| title_full | Molecular tag for promoting N-glycan maturation in the cargo receptor-mediated secretion pathway |
| title_fullStr | Molecular tag for promoting N-glycan maturation in the cargo receptor-mediated secretion pathway |
| title_full_unstemmed | Molecular tag for promoting N-glycan maturation in the cargo receptor-mediated secretion pathway |
| title_short | Molecular tag for promoting N-glycan maturation in the cargo receptor-mediated secretion pathway |
| title_sort | molecular tag for promoting n glycan maturation in the cargo receptor mediated secretion pathway |
| topic | Biochemistry Protein Properties of biomolecules Glycobiology Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224026841 |
| work_keys_str_mv | AT hirokazuyagi moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT rinoyamada moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT taikisaito moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT renahonda moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT rionakano moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT kengoinutsuka moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT seigotateo moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT hideokusano moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT kumikonishimura moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT saekoyanaka moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT takurotojima moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT akihikonakano moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT junichifurukawa moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT mahoyagiutsumi moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT shungoadachi moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway AT koichikato moleculartagforpromotingnglycanmaturationinthecargoreceptormediatedsecretionpathway |