RRC ID 12242
Author Lu N, Shen Q, Mahoney TR, Liu X, Zhou Z.
Title Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling.
Journal Mol Biol Cell
Abstract Apoptotic cells are swiftly engulfed by phagocytes and degraded inside phagosomes. Phagosome maturation requires phosphatidylinositol 3-phosphate [PtdIns(3)P], yet how PtdIns(3)P triggers phagosome maturation remains largely unknown. Through a genomewide PtdIns(3)P effector screen in the nematode Caenorhabditis elegans , we identified LST-4/SNX9, SNX-1, and SNX-6, three BAR domain-containing sorting nexins, that act in two parallel pathways to drive PtdIns(3)P-mediated degradation of apoptotic cells. We found that these proteins were enriched on phagosomal surfaces through association with PtdIns(3)P and through specific protein-protein interaction, and they promoted the fusion of early endosomes and lysosomes to phagosomes, events essential for phagosome maturation. Specifically, LST-4 interacts with DYN-1 (dynamin), an essential phagosome maturation initiator, to strengthen DYN-1's association to phagosomal surfaces, and facilitates the maintenance of the RAB-7 GTPase on phagosomal surfaces. Furthermore, both LST-4 and SNX-1 promote the extension of phagosomal tubules to facilitate the docking and fusion of intracellular vesicles. Our findings identify the critical and differential functions of two groups of sorting nexins in phagosome maturation and reveal a signaling cascade initiated by phagocytic receptor CED-1, mediated by PtdIns(3)P, and executed through these sorting nexins to degrade apoptotic cells.
Volume 22(3)
Pages 354-74
Published 2011-2-1
DOI 10.1091/mbc.E10-09-0756
PII mbc.E10-09-0756
PMID 21148288
PMC PMC3031466
MeSH Animals Apoptosis* Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Dynamins / metabolism Dynamins / physiology Endosomes / metabolism Lysosomes / metabolism Membrane Proteins / metabolism Phagocytosis / physiology Phagosomes / metabolism Phosphatidylinositol Phosphates / metabolism* Signal Transduction* Sorting Nexins / genetics Sorting Nexins / metabolism Sorting Nexins / physiology*
IF 3.791
Times Cited 32
C.elegans tm2423 tm847 tm3790 tm3221 tm1595 tm389 tm3806 tm1555 tm702 tm1886 tm2404 tm933 tm4031 tm3171 tm3643 tm1320 tm1523