Sec22b regulates phagosome maturation by promoting ORP8-mediated lipid exchange at endoplasmic reticulum-phagosome contact sites

Article Article scientifique Article Sec22b regulates phagosome maturation by promoting ORP8-mediated lipid exchange at endoplasmic reticulum-phagosome contact sites eng 2023-10-04 2023-10-04 author Criado Santos Nina 868630 author Bouvet Samuel 820477 author Cruz Cobo María 0000-0001-5805-4392 941077 Département de pathologie et immunologie (PATIM) author Mandavit Marion 402393 author Bermont Flavien 813768 author Castelbou Cyril 30263 Département de physiologie cellulaire et métabolisme (PHYME) author Mansour Farah 0000-0002-1529-3470 922924 author Azam Maral 0000-0002-6165-1726 841595 Département de pathologie et immunologie (PATIM) author Giordano Francesca 0000-0002-5942-1753 author Nunes-Hasler Paula 0000-0002-4598-685X 707324 Département de pathologie et immunologie (PATIM) 1008 10.1038/s42003-023-05382-0 37794132 2399-3642 https://www.nature.com/articles/s42003-023-05382-0 Phagosome maturation is critical for immune defense, defining whether ingested material is destroyed or converted into antigens. Sec22b regulates phagosome maturation, yet how has remained unclear. Here we show Sec22b tethers endoplasmic reticulum-phagosome membrane contact sites (MCS) independently of the known tether STIM1. Sec22b knockdown increases calcium signaling, phagolysosome fusion and antigen degradation and alters phagosomal phospholipids PI(3)P, PS and PI(4)P. Levels of PI(4)P, a lysosome docking lipid, are rescued by Sec22b re-expression and by expression of the artificial tether MAPPER but not the MCS-disrupting mutant Sec22b-P33. Moreover, Sec22b co-precipitates with the PS/PI(4)P exchange protein ORP8. Wild-type, but not mutant ORP8 rescues phagosomal PI(4)P and reduces antigen degradation. Sec22b, MAPPER and ORP8 but not P33 or mutant-ORP8 restores phagolysosome fusion in knockdown cells. These findings clarify an alternative mechanism through which Sec22b controls phagosome maturation and beg a reassessment of the relative contribution of Sec22b-mediated fusion versus tethering to phagosome biology. ER ER-to-Golgi intermediate compartment ERGIC ERS24 Osbpl5 Osbpl8 Phosphoinositide Phosphatidylinositol Dewey 612 Dewey 616.07 Swiss National Science Foundation Exploring the ER-phagosome connection during antigen cross-presentation 189094 CH Projects 137 Département de pathologie et immunologie 21F 134 Département de physiologie cellulaire et métabolisme 21C false 1293 Mécanismes de la présentation croisée des antigènes 1011 168 Signaux intracellulaires 210 https://doi.org/10.26037/yareta:d6bpvmpn4rfchkw6mduh3woq3u Communications biology 6 1 6599458c-8794-4f3b-b52d-9e5b2ba8ca54 Article (Published version) Public Article-scientifique-from-crossref.pdf 10042765 application/pdf CC BY-4.0 32fb691342a5d83d50c5de374793aeb8e0ae17d6ae38d016745ce912c7d302b0 871991fc-f5c5-4214-8f9f-e95d072949ba Supplemental data Public SupplementaryFigures_Revised_F_v3.pdf 1896560 application/pdf CC BY-4.0 afff50c82dd34cf49d1b794c748458874fd6743e45eb23a3df849cc340b6014f e38d1739-c329-4599-b11f-5e53fa29566b Supplemental data Public 42003_2023_5382_MOESM4_ESM.xlsx 273318 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet e96050a0b7608345c6c446010a80271e091fc7e7438b1f60e819e7d16781b4ce openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

Title	Published in	Year	Views	Downloads

Sec22b regulates phagosome maturation by promoting ORP8-mediated lipid exchange at endoplasmic reticulum-phagosome contact sites	Communications biology	2023	180	62
Investigating the role of Sec22b on phagolysosome fusion regulation		2022	80	0

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Mansour, Farah