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

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

doi:http://dx.doi.org/10.1038/s41467-023-39277-9

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

Llicència

Citació

Wojnacki J, Lujan AL, Brouwers N, Aranda-Vallejo C, Bigliani G, Pena Rodriguez M, Foresti O, Malhotra V. Tetraspanin-8 sequesters syntaxin-2 to control biphasic release propensity of mucin granules. Nat Commun. 2023 Jun 22;14(1):3710. DOI: 10.1038/s41467-023-39277-9

Resum

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.