Skip to Main content Skip to Navigation
Journal articles

Pannexin‐1 limits the production of proinflammatory cytokines during necroptosis

Tiphaine Douanne 1, 2, 3 Gwennan André-Grégoire 1, 2, 3, 4 Kilian Trillet 1, 2, 3 An Thys 1, 2, 3 Antonin Papin 5, 2, 3 Magalie Feyeux 6 Philippe Hulin 6 David Chiron 5, 2, 3 Julie Gavard 1, 2, 3, 4 Nicolas Bidère 1, 2, 3, * 
Abstract : The activation of mixed lineage kinase-like (MLKL) by receptor-interacting protein kinase-3 (RIPK3) controls the execution of necroptosis, a regulated form of necrosis that occurs in apopto-sis-deficient conditions. Active oligomerized MLKL triggers the exposure of phosphatidylserine residues on the cell surface and disrupts the plasma membrane integrity by forming lytic pores. MLKL also governs endosomal trafficking and biogenesis of small extracellular vesicles as well as the production of proin-flammatory cytokines during the early steps of necroptosis; however, the molecular basis continues to be elucidated. Here, we find that MLKL oligomers activate Pannexin-1 (PANX1) channels , concomitantly to the loss of phosphatidylserine asymmetry. This plasma membrane "leakiness" requires the small GTPase RAB27A and RAB27B isoforms, which regulate intracellu-lar vesicle trafficking, docking, and fusion with the plasma membrane. Although cells in which PANX1 is silenced or inhibited normally undergo necroptotic death, they display enhanced production of cytokines such as interleukin-8, indicating that PANX1 may tamper with inflammation. These data identify a novel signaling nexus between MLKL, RAB27, and PANX1 and propose ways to interfere with inflammation associated with necroptosis.
Document type :
Journal articles
Complete list of metadata

Cited literature [49 references]  Display  Hide  Download
Contributor : Elizabeth Bernardo Connect in order to contact the contributor
Submitted on : Monday, September 9, 2019 - 9:27:20 AM
Last modification on : Wednesday, April 27, 2022 - 3:59:53 AM
Long-term archiving on: : Friday, February 7, 2020 - 10:24:45 AM


 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document



Tiphaine Douanne, Gwennan André-Grégoire, Kilian Trillet, An Thys, Antonin Papin, et al.. Pannexin‐1 limits the production of proinflammatory cytokines during necroptosis. EMBO Reports, EMBO Press, 2019, pp.e47840. ⟨10.15252/embr.201947840⟩. ⟨inserm-02281304⟩



Record views