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Membrane curvature regulates the spatial distribution of bulky glycoproteins

Author

Listed:
  • Chih-Hao Lu

    (Department of Chemistry, Stanford University)

  • Kayvon Pedram

    (Department of Chemistry, Stanford University
    Howard Hughes Medical Institute)

  • Ching-Ting Tsai

    (Department of Chemistry, Stanford University)

  • Taylor Jones

    (Department of Chemistry, Stanford University)

  • Xiao Li

    (Department of Chemistry, Stanford University
    Xi’an Jiaotong University)

  • Melissa L. Nakamoto

    (Department of Chemistry, Stanford University)

  • Carolyn R. Bertozzi

    (Department of Chemistry, Stanford University
    Stanford ChEM-H, Stanford University
    Howard Hughes Medical Institute, Stanford University)

  • Bianxiao Cui

    (Department of Chemistry, Stanford University)

Abstract

The glycocalyx is a shell of heavily glycosylated proteins and lipids distributed on the cell surface of nearly all cell types. Recently, it has been found that bulky transmembrane glycoproteins such as MUC1 can modulate membrane shape by inducing membrane protrusions. In this work, we examine the reciprocal relationship of how membrane shape affects MUC1’s spatial distribution on the cell membrane and its biological significance. By employing nanopatterned surfaces and membrane-sculpting proteins to manipulate membrane curvature, we show that MUC1 avoids positively-curved membranes (membrane invaginations) and accumulates on negatively-curved membranes (membrane protrusions). MUC1’s curvature sensitivity is dependent on the length and the extent of glycosylation of its ectodomain, with large and highly glycosylated forms preferentially staying out of positive curvature. Interestingly, MUC1’s avoidance of positive membrane curvature enables it to escape from endocytosis and being removed from the cell membrane. These findings also suggest that the truncation of MUC1’s ectodomain, often observed in breast and ovarian cancers, may enhance its endocytosis and potentiate its intracellular accumulation and signaling.

Suggested Citation

  • Chih-Hao Lu & Kayvon Pedram & Ching-Ting Tsai & Taylor Jones & Xiao Li & Melissa L. Nakamoto & Carolyn R. Bertozzi & Bianxiao Cui, 2022. "Membrane curvature regulates the spatial distribution of bulky glycoproteins," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30610-2
    DOI: 10.1038/s41467-022-30610-2
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    References listed on IDEAS

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    1. Matthew J. Paszek & Christopher C. DuFort & Olivier Rossier & Russell Bainer & Janna K. Mouw & Kamil Godula & Jason E. Hudak & Jonathon N. Lakins & Amanda C. Wijekoon & Luke Cassereau & Matthew G. Rub, 2014. "The cancer glycocalyx mechanically primes integrin-mediated growth and survival," Nature, Nature, vol. 511(7509), pages 319-325, July.
    2. Wade F. Zeno & Upayan Baul & Wilton T. Snead & Andre C. M. DeGroot & Liping Wang & Eileen M. Lafer & D. Thirumalai & Jeanne C. Stachowiak, 2018. "Synergy between intrinsically disordered domains and structured proteins amplifies membrane curvature sensing," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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    1. Haoqing Jerry Wang & Yao Wang & Seyed Sajad Mirjavadi & Tomas Andersen & Laura Moldovan & Parham Vatankhah & Blake Russell & Jasmine Jin & Zijing Zhou & Qing Li & Charles D. Cox & Qian Peter Su & Lini, 2024. "Microscale geometrical modulation of PIEZO1 mediated mechanosensing through cytoskeletal redistribution," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Joann Chongsaritsinsuk & Alexandra D. Steigmeyer & Keira E. Mahoney & Mia A. Rosenfeld & Taryn M. Lucas & Courtney M. Smith & Alice Li & Deniz Ince & Fiona L. Kearns & Alexandria S. Battison & Marie A, 2023. "Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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