A Phosphoinositide Switch Controls the Maturation and Signaling Properties of APPL Endosomes

Zoncu, Roberto; Perera, Rushika M.; Balkin, Daniel M.; Pirruccello, Michelle; Toomre, Derek; Camilli, Pietro De

doi:10.1016/j.cell.2009.01.032

Cited by 322 publications

(466 citation statements)

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“…For example, switching from PIP 2 to PIP 3 is a crucial phenomenon during the maturation of macropinocytosis [11]. On the other hand, a recent report showed that loss of PIP 3 paradoxically proceeds the acquisition of phosphatidylinositol 3-phosphate in some vesicular compartments [37]. We thus postulate that the Ras-PI3K signaling pathway specifically participates in the maturation of these internal vesicles, where the Ras and PI3K complex resides.…”

Section: Discussionmentioning

confidence: 80%

Visualization of Ras-PI3K interaction in the endosome using BiFC

Tsutsumi¹,

Fujioka²,

Tsuda³

et al. 2009

Cellular Signalling

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Section: Discussionmentioning

confidence: 80%

Visualization of Ras-PI3K interaction in the endosome using BiFC

Tsutsumi¹,

Fujioka²,

Tsuda³

et al. 2009

Cellular Signalling

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“…PIs are essential for the progressive maturation of endosomes and macropinosomes 52, 53. When cells expressing the PtdIns(3)P probe EGFP‐FYVE EEA1 were infected with WR mCherry‐A4 MVs and analyzed 15 min after warming by confocal microscopy, about 16.0% of the viruses were located in PtdIns(3)P‐positive vacuoles (Figure 4A,B).…”

Section: Resultsmentioning

confidence: 99%

Vaccinia Virus Infection Requires Maturation of Macropinosomes

Rizopoulos

Balistreri

Kilcher

et al. 2015

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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.

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“…Furthermore, early and recycling endosomes remained clearly separated in MTM1-depleted and control cells, indicating that progression from early to recycling endosomes together with compartmental identity and segregation remained unaffected (Figure 17). In contrast, TfR-cluster in MTM1-depleted cells were devoid of late endosomal/ lysosomal marker LAMP1, Rab35, a marker for fast recycling to the cell surface (Kouranti, Sachse et al 2006), APPL1, a marker for signaling endosomes (Zoncu, Perera et al 2009), endocytic adaptor proteins such as AP-2, retromer components involved in retrograde endosome-toGolgi transport (i.e. Vps26, (Bonifacino and Hurley 2008)) or the Golgi marker GM130 (Figure 16a-c).…”

Section: Sub-plasma Membrane Early and Recycling Endosomes Accumulatementioning

confidence: 99%

A phosphoinositide conversion mechanism for exit from endosomes

Ketel¹,

Krauß²,

Nicot³

et al. 2016

Nature

157

177

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I owe special thanks to Marnix Wieffer and Michael Krauß, who spent a lot of time helping me to get started in the lab, to overcome numerous experimental problem, I was not sure how to deal with, and frequently joined in discussions about my project with excellent advice. I am really grateful for your experimental support, Michael, and the time you invested in the project during our paper revision.Further, I would like to thank Jocelyn Laporte and his group, especially Anne-Sophie Nicot, at the IGBMC in Strasbourg for their support and a very fruitful collaboration, and Carsten Schultz and his group at the EMBL in Heidelberg for their support and constant supply with PIP/AMs. I owe special thanks to Dmytro Puchkov for the ultrastructural analysis and Eberhard Krause for mass spectrometry done within this project. I also need to acknowledge Markus Wenk and Federico Torta at the Singapore Lipidomics Incubator for joining the project at a very late stage, when we urgently needed help from lipidomics specialists. It was a pity that experiments did not work out as planned.I would further like to express my gratitude to two very skilled technicians in the AG Haucke lab: Silke Zillmann and Delia Löwe. Without your help it would have been impossible to achieve so much within the limited amount of time I had during the paper revision. by VPS34-IN1 treatment................................................... 52 2.3.11 Fluorescence microscopy................................................................................. 53 2.3.12 Flow cytometry............................................................................................ III SummaryPhosphoinositides (PIs) are a minor class of short-lived phospholipids that serve as crucial signposts of membrane identity. Thereby, PIs full fill important functions in cell signaling and membrane transport. PI 4-phosphates such as phosphatitylinositol-4-phosphate (PI(4)P) and phosphatitylinositol-4,5-bisphosphate (PI(4,5)P 2 ) are enriched at the plasma membrane (PM), on secretory organelles and lysosomes, while PI 3-phosphates, i.e.phosphatitylinositol-3-phosphate (PI(3)P), are a hallmark of the endosomal system.Directional transport between these compartments, thus, requires regulated PI conversion.However, PI conversion in exit from PI(3)P-enriched endosomes en route to the PI(4)P-and PI(4,5)P 2 -positive PM in endosomal recycling remained unknown.Here, we report that cargo exit from endosomes requires removal of PI(3)P by the PI(3)P 3-phosphatase myotubularin 1 (MTM1), and concomitant PI(4)P synthesis by PI 4-kinase type II α (PI4K2α). Loss of MTM1 causes endosomal accumulation of PI(3)P and PI(3)P effector proteins, i.e. sorting nexins, Kif16b-mediated outward traffic of PI(3)P containing endosomes and sub-plasmalemmal accumulation of exocytosis-deficient endosomes. As PI4K2α associates with MTM1 and thereby facilitates membrane recruitment of MTM1, these phenotypic changes are mimicked by loss of PI4K2α. The conversion of PI(3)P-to-PI(4)P is paralleled by a switch i...

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A Phosphoinositide Switch Controls the Maturation and Signaling Properties of APPL Endosomes

Cited by 322 publications

References 51 publications

Visualization of Ras-PI3K interaction in the endosome using BiFC

Visualization of Ras-PI3K interaction in the endosome using BiFC

Vaccinia Virus Infection Requires Maturation of Macropinosomes

A phosphoinositide conversion mechanism for exit from endosomes

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