Phosphoinositides in phagocytosis and macropinocytosis

Levin, Roni; Grinstein, Sergio; Schlam, Daniel

doi:10.1016/j.bbalip.2014.09.005

Cited by 133 publications

(135 citation statements)

References 188 publications

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…PI kinases also play a central role in regulating the maturation of endosomes, phagosomes and macropinosomes 67. Our RNAi screen indicated that PI(3)K, PI(4)K, PI(5)K and PIKfyve were needed for MV infection (Figure 2).…”

Section: Discussionmentioning

confidence: 94%

Vaccinia Virus Infection Requires Maturation of Macropinosomes

Rizopoulos

Balistreri

Kilcher

et al. 2015

Traffic

View full text Add to dashboard Cite

The prototypic poxvirus, vaccinia virus (VACV), occurs in two infectious forms, mature virions (MVs) and extracellular virions (EVs). Both enter HeLa cells by inducing macropinocytic uptake. Using confocal microscopy, live‐cell imaging, targeted RNAi screening and perturbants of endosome maturation, we analyzed the properties and maturation pathway of the macropinocytic vacuoles containing VACV MVs in HeLa cells. The vacuoles first acquired markers of early endosomes [Rab5, early endosome antigen 1 and phosphatidylinositol(3)P]. Prior to release of virus cores into the cytoplasm, they contained markers of late endosomes and lysosomes (Rab7a, lysosome‐associated membrane protein 1 and sorting nexin 3). RNAi screening of endocytic cell factors emphasized the importance of late compartments for VACV infection. Follow‐up perturbation analysis showed that infection required Rab7a and PIKfyve, confirming that VACV is a late‐penetrating virus dependent on macropinosome maturation. VACV EV infection was inhibited by depletion of many of the same factors, indicating that both infectious particle forms share the need for late vacuolar conditions for penetration.

show abstract

Section: Discussionmentioning

confidence: 94%

Vaccinia Virus Infection Requires Maturation of Macropinosomes

Rizopoulos

Balistreri

Kilcher

et al. 2015

Traffic

View full text Add to dashboard Cite

show abstract

“…Specific kinases and phosphatases control their spatial and temporal distribution, allowing a precise and local modulation of essential processes including endocytosis and phagocytosis, membrane traffic, and autophagy (31)(32)(33). These processes are commonly manipulated by bacterial pathogens to invade, survive, and replicate within host cells.…”

Section: Discussionmentioning

confidence: 99%

Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development

Martínez

Allombert

Cantet

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

129

View full text Add to dashboard Cite

The Q fever bacterium Coxiella burnetii replicates inside host cells within a large Coxiella-containing vacuole (CCV) whose biogenesis relies on the Dot/Icm-dependent secretion of bacterial effectors. Several membrane trafficking pathways contribute membranes, proteins, and lipids for CCV biogenesis. These include the endocytic and autophagy pathways, which are characterized by phosphatidylinositol 3-phosphate [PI(3)P]-positive membranes. Here we show that the C. burnetii secreted effector Coxiella vacuolar protein B (CvpB) binds PI(3)P and phosphatidylserine (PS) on CCVs and early endosomal compartments and perturbs the activity of the phosphatidylinositol 5-kinase PIKfyve to manipulate PI(3)P metabolism. CvpB association to early endosome triggers vacuolation and clustering, leading to the channeling of large PI(3)P-positive membranes to CCVs for vacuole expansion. At CCVs, CvpB binding to early endosome-and autophagy-derived PI(3)P and the concomitant inhibition of PIKfyve favor the association of the autophagosomal machinery to CCVs for optimal homotypic fusion of the Coxiella-containing compartments. The importance of manipulating PI(3)P metabolism is highlighted by mutations in cvpB resulting in a multivacuolar phenotype, rescuable by gene complementation, indicative of a defect in CCV biogenesis. Using the insect model Galleria mellonella, we demonstrate the in vivo relevance of defective CCV biogenesis by highlighting an attenuated virulence phenotype associated with cvpB mutations.Coxiella burnetii | host-pathogen interactions | phosphoinositides

show abstract

“…It is alluring to speculate that signal transduction from upstream receptors may involve protein kinases including Src and Syk, that in turn may regulate the PI3KC3 complex upon LAP initiation through specific post-translation modifications. Inositide signaling can regulate early phagocytic events [40, 41] and diacyl-glycerol, produced by phospholipase C (PLC) from PI(4,5)P 2 after phagosome closure, regulates ROS production and phagosome LC3 conjugation in response to Listeria monocytogenes [42] and Legionella dumoffii [43] infections. Whether these signaling moieties participate in all LAP-mediated processes is currently unknown.…”

Section: Pi3k and Rubicon Are Required For Lapmentioning

confidence: 99%

LC3-Associated Phagocytosis and Inflammation

Heckmann

Boada-Romero

Cunha

et al. 2017

Journal of Molecular Biology

216

202

View full text Add to dashboard Cite

LC3-associated phagocytosis (LAP) is a novel form of non-canonical autophagy where LC3 (microtubule-associated protein 1A/1B-light chain 3) is conjugated to phagosome membranes using a portion of the canonical autophagy machinery. The impact of LAP to immune regulation is best characterized in professional phagocytes, in particular macrophages, where LAP has instrumental roles in the clearance of extracellular particles including apoptotic cells and pathogens. Binding of dead cells via receptors present on the macrophage surface results in the translocation of the autophagy machinery to the phagosome and ultimately LC3 conjugation. These events promote a rapid form of phagocytosis that produces an “immunologically silent” clearance of the apoptotic cells. Consequences of LAP deficiency include a decreased capacity to clear dying cells and the establishment of a lupus-like autoimmune disease in mice. The ability of LAP to attenuate autoimmunity likely occurs through the dampening of pro-inflammatory signals upon engulfment of dying cells and prevention of autoantigen presentation to other immune cells. However, it remains unclear how LAP shapes both the activation and outcome of the immune response at the molecular level. Herein, we provide a detailed review of LAP and its known roles in the immune response and provide further speculation on the putative mechanisms by which LAP may regulate immune function, perhaps through the metabolic reprogramming and polarization of macrophages.

show abstract

Phosphoinositides in phagocytosis and macropinocytosis

Cited by 133 publications

References 188 publications

Vaccinia Virus Infection Requires Maturation of Macropinosomes

Vaccinia Virus Infection Requires Maturation of Macropinosomes

Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development

LC3-Associated Phagocytosis and Inflammation

Contact Info

Product

Resources

About