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Tetraspanin-8 sequesters syntaxin-2 to control biphasic release propensity of mucin granules

Author

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  • José Wojnacki

    (The Barcelona Institute for Science and Technology)

  • Agustin Leonardo Lujan

    (The Barcelona Institute for Science and Technology)

  • Nathalie Brouwers

    (The Barcelona Institute for Science and Technology)

  • Carla Aranda-Vallejo

    (The Barcelona Institute for Science and Technology
    Universitat Pompeu Fabra (UPF))

  • Gonzalo Bigliani

    (The Barcelona Institute for Science and Technology)

  • Maria Pena Rodriguez

    (The Barcelona Institute for Science and Technology)

  • Ombretta Foresti

    (The Barcelona Institute for Science and Technology)

  • Vivek Malhotra

    (The Barcelona Institute for Science and Technology
    Universitat Pompeu Fabra (UPF)
    ICREA)

Abstract

Agonist-mediated stimulated pathway of mucin and insulin release are biphasic in which rapid fusion of pre-docked granules is followed by slow docking and fusion of granules from the reserve pool. Here, based on a cell-culture system, we show that plasma membrane-located tetraspanin-8 sequesters syntaxin-2 to control mucin release. Tetraspanin-8 affects fusion of granules during the second phase of stimulated mucin release. The tetraspanin-8/syntaxin-2 complex does not contain VAMP-8, which functions with syntaxin-2 to mediate granule fusion. We suggest that by sequestering syntaxin-2, tetraspanin-8 prevents docking of granules from the reserve pool. In the absence of tetraspanin-8, more syntaxin-2 is available for docking and fusion of granules and thus doubles the quantities of mucins secreted. This principle also applies to insulin release and we suggest a cell type specific Tetraspanin/Syntaxin combination is a general mechanism regulating the fusion of dense core granules.

Suggested Citation

  • José Wojnacki & Agustin Leonardo Lujan & Nathalie Brouwers & Carla Aranda-Vallejo & Gonzalo Bigliani & Maria Pena Rodriguez & Ombretta Foresti & Vivek Malhotra, 2023. "Tetraspanin-8 sequesters syntaxin-2 to control biphasic release propensity of mucin granules," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39277-9
    DOI: 10.1038/s41467-023-39277-9
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    References listed on IDEAS

    as
    1. Reinhard Jahn & Dirk Fasshauer, 2012. "Molecular machines governing exocytosis of synaptic vesicles," Nature, Nature, vol. 490(7419), pages 201-207, October.
    2. Steve Cornick & Manish Kumar & France Moreau & Herbert Gaisano & Kris Chadee, 2019. "VAMP8-mediated MUC2 mucin exocytosis from colonic goblet cells maintains innate intestinal homeostasis," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    3. Ying Lai & Giorgio Fois & Jose R. Flores & Michael J. Tuvim & Qiangjun Zhou & Kailu Yang & Jeremy Leitz & John Peters & Yunxiang Zhang & Richard A. Pfuetzner & Luis Esquivies & Philip Jones & Manfred , 2022. "Inhibition of calcium-triggered secretion by hydrocarbon-stapled peptides," Nature, Nature, vol. 603(7903), pages 949-956, March.
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