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

José Wojnacki, Agustin Leonardo Lujan, Nathalie Brouwers, Carla Aranda-Vallejo, Gonzalo Bigliani, Maria Pena Rodriguez, Ombretta Foresti and Vivek Malhotra ()
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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
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

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39277-9

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