Lipids regulate P2X7-receptor-dependent actin assembly by phagosomes via ADP translocation and ATP synthesis in the phagosome lumen

Author:

Kuehnel Mark. P.1,Rybin Vladimir1,Anand Paras K.1,Anes Elsa2,Griffiths Gareth1

Affiliation:

1. EMBL, Meyerhofstr. 1, 69117 Heidelberg, Germany

2. Molecular Pathogenesis Centre, Unit of Retrovirus and Associated Infections, Faculty of Pharmacy, University of Lisbon, Av. Forcas Armadas, 1600-083 Lisbon, Portugal

Abstract

Latex bead phagosomes isolated from J774 macrophages polymerize actin. We show here that five lipids – phosphatidylinositol-4-phosphate, phosphatidylinositol-(4,5)-bisphosphate, sphingosine-1-phosphate (S1P), ceramide-1-phosphate and phosphatidic acid – stimulate both actin assembly and transport of ADP across the phagosomal membrane into the lumen. Once there, this ADP is converted to ATP by adenylate kinase activity. High luminal ATP concentrations correlated well with phagosome actin assembly under different conditions. The ATP-binding P2X7 receptor (P2X7R) was detected in phagosomes. Although S1P stimulated actin assembly by phagosomes from P2X7R-containing bone marrow macrophages, S1P-stimulated actin assembly was inhibited in phagosomes from cells lacking P2X7R. We propose that luminal ATP accumulates in response to selected lipids and activates the P2X7R that signals across the phagosomal membrane to trigger actin assembly on the cytoplasmic membrane surface. In the accompanying paper by Kuehnel et al. (doi:10.1242/jcs.034207), more evidence is provided in support of this model from the analysis of actin assembly at the plasma membrane of intact macrophages.

Publisher

The Company of Biologists

Subject

Cell Biology

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