Contribution of phosphatidylserine to membrane surface charge and protein targeting during phagosome maturation |
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Authors: | Tony Yeung Bryan Heit Jean-Francois Dubuisson Gregory D Fairn Basil Chiu Robert Inman Andras Kapus Michele Swanson Sergio Grinstein |
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Institution: | 1.Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada;2.Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109;3.Department of Medicine, Division of Rheumatology, University Health Network, University of Toronto, Toronto, Ontario M5T 2S8, Canada;4.St. Michael’s Hospital Research Institute, Toronto, Ontario M5B 1W8, Canada |
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Abstract: | During phagocytosis, the phosphoinositide content of the activated membrane decreases sharply, as does the associated surface charge, which attracts polycationic proteins. The cytosolic leaflet of the plasma membrane is enriched in phosphatidylserine (PS); however, a lack of suitable probes has precluded investigation of the fate of this phospholipid during phagocytosis. We used a recently developed fluorescent biosensor to monitor the distribution and dynamics of PS during phagosome formation and maturation. Unlike the polyphosphoinositides, PS persists on phagosomes after sealing even when other plasmalemmal components have been depleted. High PS levels are maintained through fusion with endosomes and lysosomes and suffice to attract cationic proteins like c-Src to maturing phagosomes. Phagocytic vacuoles containing the pathogens Legionella pneumophila and Chlamydia trachomatis, which divert maturation away from the endolysosomal pathway, are devoid of PS, have little surface charge, and fail to recruit c-Src. These findings highlight a function for PS in phagosome maturation and microbial killing. |
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