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Publication : Kinesin 5B is necessary for delivery of membrane and receptors during FcγR-mediated phagocytosis.

First Author  Silver KE Year  2011
Journal  J Immunol Volume  186
Issue  2 Pages  816-25
PubMed ID  21149599 Mgi Jnum  J:168777
Mgi Id  MGI:4938223 Doi  10.4049/jimmunol.1002161
Citation  Silver KE, et al. (2011) Kinesin 5B is necessary for delivery of membrane and receptors during FcgammaR-mediated phagocytosis. J Immunol 186(2):816-25
abstractText  FcgammaR-mediated phagocytosis is a cellular event that is evolutionary conserved to digest IgG-opsonized pathogens. Pseudopod formation during phagocytosis is a limiting step in managing the uptake of particles, and in this paper, we show that the conventional kinesin is involved in both receptor and membrane delivery to the phagocytic cup. Expression of a mutant kinesin isoform (GFP dominant negative mutant of kinesin H chain [EGFP-Kif5B-DN]) in RAW264.7 cells significantly reduced binding of IgG-sheep RBCs when macrophages were faced with multiple encounters with opsonized particles. Scanning electron microscopy analysis of EGFP-Kif5B-DN-expressing cells challenged with two rounds of IgG-sheep RBCs showed sparse, extremely thin pseudopods. We saw disrupted Rab11 trafficking to the phagocytic cup in EGFP-Kif5B-DN-transfected cells. Our particle overload assays also implicated phagosome membrane recycling in pseudopod formation. We observed reduced phagosome fission and trafficking in mutant kinesin-expressing cells, as well as reduced cell surface expression of FcgammaRs and Mac-1 receptors. In conclusion, anterograde trafficking via kinesin is essential for both receptor recycling from the phagosome and delivery of Rab11-containing membrane stores to effect broad and functional pseudopods during FcgammaR-mediated phagocytosis.
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