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Multiphasic dynamics of phosphatidylinositol 4-phosphate during phagocytosis
#MMPMID28035045
Levin R
; Hammond GR
; Balla T
; De Camilli P
; Fairn GD
; Grinstein S
Mol Biol Cell
2017[Jan]; 28
(1
): 128-140
PMID28035045
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We analyzed the distribution, fate, and functional role of phosphatidylinositol
4-phosphate (PtdIns4P) during phagosome formation and maturation. To this end, we
used genetically encoded probes consisting of the PtdIns4P-binding domain of the
bacterial effector SidM. PtdIns4P was found to undergo complex, multiphasic
changes during phagocytosis. The phosphoinositide, which is present in the
plasmalemma before engagement of the target particle, is transiently enriched in
the phagosomal cup. Soon after the phagosome seals, PtdIns4P levels drop
precipitously due to the hydrolytic activity of Sac2 and phospholipase C,
becoming undetectable for ?10 min. PtdIns4P disappearance coincides with the
emergence of phagosomal PtdIns3P. Conversely, the disappearance of PtdIns3P that
signals the transition from early to late phagosomes is accompanied by resurgence
of PtdIns4P, which is associated with the recruitment of phosphatidylinositol
4-kinase 2A. The reacquisition of PtdIns4P can be prevented by silencing
expression of the kinase and can be counteracted by recruitment of a
4-phosphatase with a heterodimerization system. Using these approaches, we found
that the secondary accumulation of PtdIns4P is required for proper phagosomal
acidification. Defective acidification may be caused by impaired recruitment of
Rab7 effectors, including RILP, which were shown earlier to displace phagosomes
toward perinuclear lysosomes. Our results show multimodal dynamics of PtdIns4P
during phagocytosis and suggest that the phosphoinositide plays important roles
during the maturation of the phagosome.
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