Kinesin-1 controls mast cell degranulation and anaphylaxis through PI3K-dependent recruitment to the granular Slp3/Rab27b complex : Kinesin-1 regulates mast cell degranulation

Isabelle Munoz 1 Luca Danelli 2 Julien Claver 2 Nicolas Goudin 3 Mathieu Kurowska 1 Iris Karina Madera-Salcedo 2 Jian-Dong Huang 1, 4 Alain Fischer 5, 1, 6 Claudia González-Espinosa 1 Geneviève De Saint Basile 1 Ulrich Blank 2 Gaël Ménasché 1, *
* Auteur correspondant
1 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
2 CRI - Centre de recherche sur l'Inflammation
3 Plateforme d'Imagerie Cellulaire [Necker]
SFR Necker - UMS 3633 / US24 - Structure Fédérative de Recherche Necker
4 School of Biomedical Science [Hong Kong, China]
5 CDF - Collège de France
6 Service d'Immunologie et d'Hématologie Pédiatriques [AP-HP Hôpital Necker-Enfants malades]
Abstract : Cross-linking of mast cell IgE receptors (FcRI) triggers degranulation of secretory granules (SGs) and the release of many allergic and inflammatory mediators. Although degranulation depends crucially on microtubule dynamics, the molecular machinery that couples SGs to microtubule-dependent transport is poorly understood. Here, we demonstrate that mice lacking Kif5b (the heavy chain of kinesin-1) in hematopoietic cells are less sensitive to IgE-mediated, passive, systemic anaphylaxis. After IgE-induced stimulation, bone-marrow-derived mast cells from Kif5b-knock-out mice exhibited a marked reduction in SG translocation towards the secretion site. In contrast, a lack of Kif5b did not affect cytokine secretion, early FcRI-initiated signaling pathways or microtubule reorganization upon FcRI stimulation. We identified Slp3 as the critical effector linking kinesin-1 to Rab27b-associated SGs. Kinesin-1 recruitment to the Slp3/Rab27b effector complex was independent of microtubule reorganization but occurred only upon stimulation requiring PI3K activity. Our findings demonstrate that PI3K-dependent formation of a kinesin-1/Slp3/Rab27b complex is critical for the microtubule-dependent movement of SGs required for mast cell degranulation.
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The Journal of Cell Biology, 2016, 215 (2), pp.203-216. 〈10.1083/jcb.201605073〉
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Isabelle Munoz, Luca Danelli, Julien Claver, Nicolas Goudin, Mathieu Kurowska, et al.. Kinesin-1 controls mast cell degranulation and anaphylaxis through PI3K-dependent recruitment to the granular Slp3/Rab27b complex : Kinesin-1 regulates mast cell degranulation . The Journal of Cell Biology, 2016, 215 (2), pp.203-216. 〈10.1083/jcb.201605073〉. 〈inserm-01415529〉

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