Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 29, Issue 4, Pages 452-465Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E17-07-0464
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- Deutsche Forschungsgemeinschaft (DFG) [(SFB) 645, SPP1580]
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Phagosomes mature into phagolysosomes by sequential fusion with early endosomes, late endosomes, and lysosomes. Phagosome-with-lysosome fusion (PLF) results in the delivery of lysosomal hydrolases into phagosomes and in digestion of the cargo. The machinery that drives PLF has been little investigated. Using a cell-free system, we recently identified the phosphoinositide lipids (PIPs) phosphatidylinositol 3-phosphate (PI(3) P) and phosphatidylinositol 4-phosphate (PI(4) P) as regulators of PLF. We now report the identification and the PIP requirements of four distinct subreactions of PLF. Our data show that (i) PI(3) P and PI(4) P are dispensable for the disassembly and activation of (phago) lysosomal soluble N-ethylmaleimide- sensitive factor attachment protein receptors, that (ii) PI(3) P is required only after the tethering step, and that (iii) PI(4) P is required during and after tethering. Moreover, our data indicate that PI(4) P is needed to anchor Arl8 (Arf-like GTPase 8) and its effector homotypic fusion/vacuole protein sorting complex (HOPS) to (phago) lysosome membranes, whereas PI(3) P is required for membrane association of HOPS only. Our study provides a first link between PIPs and established regulators of membrane fusion in late endocytic trafficking.
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