RRC ID 45537
Author Cheng S, Wang K, Zou W, Miao R, Huang Y, Wang H, Wang X.
Title PtdIns(4,5)P₂ and PtdIns3P coordinate to regulate phagosomal sealing for apoptotic cell clearance.
Journal J Cell Biol
Abstract Phagocytosis requires phosphoinositides (PIs) as both signaling molecules and localization cues. How PIs coordinate to control phagosomal sealing and the accompanying switch of organelle identity is unclear. In this study, we followed dynamic changes in PIs during apoptotic cell clearance in Caenorhabditis elegans. We found that phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3-phosphate (PtdIns3P), which accumulate transiently on unsealed and fully sealed phagosomes, respectively, are both involved in phagosome closure. We identified PtdIns3P phosphatase MTM-1 as an effector of PtdIns(4,5)P2 to promote phagosomal sealing. MTM-1 coordinates with the class II PI3 kinase PIKI-1 to control PtdIns3P levels on unsealed phagosomes. The SNX9 family protein LST-4 is required for sealing, and its association with unsealed phagosomes is regulated by PtdIns(4,5)P2, PIKI-1, and MTM-1. Loss of LST-4 or its retention on phagosomes disrupts sealing and suppresses PtdIns3P accumulation, indicating close coupling of the two events. Our findings support a coincidence detection mechanism by which phagosomal sealing is regulated and coupled with conversion from PtdIns(4,5)P2 enrichment on unsealed phagosomes to PtdIns3P enrichment on fully sealed phagosomes.
Volume 210(3)
Pages 485-502
Published 2015-8-3
DOI 10.1083/jcb.201501038
PII jcb.201501038
PMID 26240185
PMC PMC4523610
MeSH Animals Apoptosis / genetics Apoptosis / physiology* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Line Class III Phosphatidylinositol 3-Kinases / genetics HEK293 Cells Humans Lysosomes / metabolism Phagocytosis / genetics Phagocytosis / physiology* Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism Phosphatidylinositol 4,5-Diphosphate / metabolism* Phosphatidylinositol Phosphates / metabolism* Phosphoric Monoester Hydrolases / genetics Phosphoric Monoester Hydrolases / metabolism RNA Interference RNA, Small Interfering Sorting Nexins / genetics Sorting Nexins / metabolism
IF 8.891
Times Cited 22
C.elegans tm2423