Improved secretion of glycoproteins using an N-glycan-restricted passport sequence tag recognized by cargo receptor

Hirokazu Yagi, Maho Yagi-Utsumi, Rena Honda, Yusaku Ohta, Taiki Saito, Miho Nishio, Satoshi Ninagawa, Kousuke Suzuki, Takahiro Anzai, Yukiko Kamiya, Kazuhiro Aoki, Mahito Nakanishi, Tadashi Satoh and Koichi Kato ()
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Hirokazu Yagi: Nagoya City University
Maho Yagi-Utsumi: Nagoya City University
Rena Honda: Nagoya City University
Yusaku Ohta: National Institutes of Natural Sciences
Taiki Saito: Nagoya City University
Miho Nishio: Nagoya City University
Satoshi Ninagawa: National Institutes of Natural Sciences
Kousuke Suzuki: Nagoya City University
Takahiro Anzai: National Institutes of Natural Sciences
Yukiko Kamiya: National Institutes of Natural Sciences
Kazuhiro Aoki: National Institutes of Natural Sciences
Mahito Nakanishi: National Institute of Advanced Industrial Science and Technology (AIST)
Tadashi Satoh: Nagoya City University
Koichi Kato: Nagoya City University

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract MCFD2 and ERGIC-53, which are the products of causative genes of combined factor V and factor VIII deficiency, form a cargo receptor complex responsible for intracellular transport of these coagulation factors in the early secretory pathway. In this study, using an NMR technique, we successfully identified an MCFD2-binding segment from factor VIII composed of a 10 amino acid sequence that enhances its secretion. This prompted us to examine possible effects of attaching this sequence to recombinant glycoproteins on their secretion. We found that the secretion level of recombinant erythropoietin was significantly increased simply by tagging it with the passport sequence. Our findings not only provide molecular basis for the intracellular trafficking of coagulation factors and their genetic deficiency but also offer a potentially useful tool for increasing the production yields of recombinant glycoproteins of biopharmaceutical interest.

Date: 2020
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DOI: 10.1038/s41467-020-15192-1

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