Mol Biol Cell. 2017 Dec 13. pii: mbc.E17-07-0464. doi: 10.1091/mbc.E17-07-0464. [Epub ahead of print]
Sequential actions of phosphatidylinositol phosphates regulate phagosome-lysosome fusion.
Abstract
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 sub-reactions of PLF.
Our data show that
(i) PI(3)P and PI(4)P are dispensable for the disassembly and activation of (phago)lysosomal SNAREs (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 HOPS (homotypic fusion/vacuole protein sorting complex) 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.
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 sub-reactions of PLF.
Our data show that
(i) PI(3)P and PI(4)P are dispensable for the disassembly and activation of (phago)lysosomal SNAREs (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 HOPS (homotypic fusion/vacuole protein sorting complex) 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.
- PMID:
- 29237821
- DOI:
- 10.1091/mbc.E17-07-0464
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