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De Novo Glycan Display on Cell Surfaces Using HaloTag: Visualizing the Effect of the Galectin Lattice on the Lateral Diffusion and Extracellular Vesicle Loading of Glycosylated Membrane Proteins
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    De Novo Glycan Display on Cell Surfaces Using HaloTag: Visualizing the Effect of the Galectin Lattice on the Lateral Diffusion and Extracellular Vesicle Loading of Glycosylated Membrane Proteins
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    • Ayane Miura
      Ayane Miura
      Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
      More by Ayane Miura
    • Yoshiyuki Manabe*
      Yoshiyuki Manabe
      Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
      Forefront Research Center, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
      *Email: [email protected]. Phone: +81-6850-5391.
    • Kenichi G. N. Suzuki
      Kenichi G. N. Suzuki
      Institute for Glyco-core Research (iGCORE), Gifu University, Gifu 501-1193, Japan
      National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan
    • Hiroki Shomura
      Hiroki Shomura
      Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
    • Soichiro Okamura
      Soichiro Okamura
      Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
    • Asuka Shirakawa
      Asuka Shirakawa
      Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
    • Kumpei Yano
      Kumpei Yano
      Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
      More by Kumpei Yano
    • Shuto Miyake
      Shuto Miyake
      Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
      More by Shuto Miyake
    • Koki Mayusumi
      Koki Mayusumi
      Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
    • Chun-Cheng Lin
      Chun-Cheng Lin
      Department of Chemistry, National Tsing-Hua University, Hsinchu 30013, Taiwan
      Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
    • Kenta Morimoto
      Kenta Morimoto
      Department of Biological Chemistry, Graduate School of Science, Osaka Metropolitan University, 1-1, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan
    • Jojiro Ishitobi
      Jojiro Ishitobi
      Department of Biological Chemistry, Graduate School of Science, Osaka Metropolitan University, 1-1, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan
    • Ikuhiko Nakase
      Ikuhiko Nakase
      Department of Biological Chemistry, Graduate School of Science, Osaka Metropolitan University, 1-1, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan
      Department of Biological Chemistry, School of Science, Osaka Metropolitan University, 1-1, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan
    • Kenta Arai
      Kenta Arai
      Advanced ICT Research Institute, National Institute of Information and Communications Technology, 588-2 Iwaoka, Iwaoka-cho, Nishi-ku, Kobe, Hyogo 651-2492, Japan
      More by Kenta Arai
    • Shouhei Kobayashi
      Shouhei Kobayashi
      Advanced ICT Research Institute, National Institute of Information and Communications Technology, 588-2 Iwaoka, Iwaoka-cho, Nishi-ku, Kobe, Hyogo 651-2492, Japan
    • Ushio Ishikawa
      Ushio Ishikawa
      Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, 4-4-1, Komatsushima, Aoba Ward, Sendai, Miyagi 981-8558, Japan
    • Hirotaka Kanoh
      Hirotaka Kanoh
      Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, 4-4-1, Komatsushima, Aoba Ward, Sendai, Miyagi 981-8558, Japan
    • Eiji Miyoshi
      Eiji Miyoshi
      Department of Molecular Biochemistry and Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
      More by Eiji Miyoshi
    • Toshiyuki Yamaji
      Toshiyuki Yamaji
      Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan
    • Kazuya Kabayama*
      Kazuya Kabayama
      Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
      Forefront Research Center, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
      Interdisciplinary Research Center for Radiation Sciences, Institute for Radiation Sciences, Osaka University, 2-4 Yamadaoka, Suita, Osaka 565-0871, Japan
      *Email: [email protected]. Phone: +81-6850-5192.
    • Koichi Fukase*
      Koichi Fukase
      Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
      Forefront Research Center, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
      Center for Advanced Modalities and DDS, Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan
      *Email: [email protected]. Phone: +81-6850-5391.
    Other Access OptionsSupporting Information (2)

    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2024, 146, 32, 22193–22207
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jacs.4c02040
    Published July 4, 2024
    Copyright © 2024 American Chemical Society

    Abstract

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    Abstract Image

    Glycans cover the cell surface to form the glycocalyx, which governs a myriad of biological phenomena. However, understanding and regulating glycan functions is extremely challenging due to the large number of heterogeneous glycans that engage in intricate interaction networks with diverse biomolecules. Glycocalyx-editing techniques offer potent tools to probe their functions. In this study, we devised a HaloTag-based technique for glycan manipulation, which enables the introduction of chemically synthesized glycans onto a specific protein (protein of interest, POI) and concurrently incorporates fluorescent units to attach homogeneous, well-defined glycans to the fluorescence-labeled POIs. Leveraging this HaloTag-based glycan-display system, we investigated the influence of the interactions between Gal-3 and various N-glycans on protein dynamics. Our analyses revealed that glycosylation modulates the lateral diffusion of the membrane proteins in a structure-dependent manner through interaction with Gal-3, particularly in the context of the Gal-3-induced formation of the glycan network (galectin lattice). Furthermore, N-glycan attachment was also revealed to have a significant impact on the extracellular vesicle-loading of membrane proteins. Notably, our POI-specific glycan introduction does not disrupt intact glycan structures, thereby enabling a functional analysis of glycans in the presence of native glycan networks. This approach complements conventional glycan-editing methods and provides a means for uncovering the molecular underpinnings of glycan functions on the cell surface.

    Copyright © 2024 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.4c02040.

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    Cited By

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    This article is cited by 1 publications.

    1. Pritam Ghosh. Deciphering the Cell Surface Sugar‐Coating via Biochemical Pathways. Chemistry – A European Journal 2024, 30 (64) https://doi.org/10.1002/chem.202401983
    2. Koichiro M. Hirosawa, Yusuke Sato, Rinshi S. Kasai, Eriko Yamaguchi, Naoko Komura, Hiromune Ando, Ayuko Hoshino, Yasunari Yokota, Kenichi G. N. Suzuki. Uptake of small extracellular vesicles by recipient cells is facilitated by paracrine adhesion signaling. 2024https://doi.org/10.1101/2024.04.11.589012

    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2024, 146, 32, 22193–22207
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jacs.4c02040
    Published July 4, 2024
    Copyright © 2024 American Chemical Society

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