Phosphatidylinositol 4-kinase is required for endosomal trafficking and degradation of the EGF receptor

Minogue, Shane; Waugh, Mark G.; Matteis, Maria Antonietta De; Stephens, David; Berditchevski, Fedor; Hsuan, J. Justin

doi:10.1242/jcs.02752

Cited by 123 publications

(154 citation statements)

References 34 publications

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“…While in this study PI4K2β depletion did not affect AP-1 recruitment to the TGN (Wang, Wang et al 2003), others showed that PI4K2β can directly interact with AP-1 and regulate AP-1 dependent endosomal sorting of the Wnt receptor Frizzled (Fz) (Wieffer, Cibrian Uhalte et al 2013). At the level of endosomes, PI4K2α and its lipid product PI(4)P localize AP-3 to endosomes to regulates lysosomal cargo delivery (Craige, Salazar et al 2008) and early-to-late endosomal trafficking of ubiquitinated EGFR or Fz (Minogue, Waugh et al 2006;Mossinger, Wieffer et al 2012). Recently, PI4K2α was shown to associate with early endosomal VAMP3 or late endosomal VAMP7.…”

Section: Other Myotubularin Family Members Contribute To Endosomal Pimentioning

confidence: 53%

“…A candidate enzyme for PI(4)P synthesis on exocytic vesicles is PI 4-kinase type II α (PI4K2α)a member of the PI4K family previously shown to be associated with endosomes (Minogue, Waugh et al 2006;Mossinger, Wieffer et al 2012), secretory vesicles (Guo, Wenk et al 2003) and the TGN (Wang, Wang et al 2003). PI4K2α was indeed found on MTM1-positive vesicles by immunocytochemistry ( Figure 29) and associated with MTM1 in pull down assay (experiments were done in collaboration with Jocelyn Laporte and Anne-Sophie Nicot, data not shown).…”

Section: Exocytic Vesicles Acquire Pi(4)p Before Plasma Membrane Fusionmentioning

confidence: 99%

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A phosphoinositide conversion mechanism for exit from endosomes

Ketel¹,

Krauß²,

Nicot³

et al. 2016

Nature

165

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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Section: Other Myotubularin Family Members Contribute To Endosomal Pimentioning

confidence: 53%

Section: Exocytic Vesicles Acquire Pi(4)p Before Plasma Membrane Fusionmentioning

confidence: 99%

A phosphoinositide conversion mechanism for exit from endosomes

Ketel¹,

Krauß²,

Nicot³

et al. 2016

Nature

165

177

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“…Kauffmann-Zeh et al (1994) reported that EGF regulates PI4KIIa activity and is associated with ERBB-1 (EGFR), and Minogue et al (2006) showed that PI4KIIa can influence the endosomal trafficking and degradation of EGFR. However, none of these reports show a direct effect of PI4KIIa on kinase activity.…”

Section: Discussionmentioning

confidence: 99%

“…A recent report showed that PI4KIIa associates with HermanskyPudlak syndrome protein complexes (Salazar et al, 2009). PI4KIIa is necessary for endosomal trafficking and degradation of activated epidermal growth factor receptor (EGFR) (Minogue et al, 2006), and it is also a critical player in the exo-endocytic cycle of synaptic vesicles (Guo et al, 2003). The loss of PI4KIIa in mouse causes late onset degeneration of spinal cord axons (Simons et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

PI4KIIα is a novel regulator of tumor growth by its action on angiogenesis and HIF-1α regulation

Zhang

et al. 2010

Oncogene

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“…Type IIα and IIβ PI4Ks are membrane-bound proteins due to the palmitoylation of a conserved stretch of cysteines in their catalytic domains (24). Immunocytochemical analysis has revealed that they are mostly associated with trans-Golgi, endoplasmic reticulum, and endosomal membranes (25)(26)(27). These type IIα and IIβ enzymes are blocked by adenosine and calcium, but are resistant to wortmannin.…”

mentioning

confidence: 99%

Golgi and plasma membrane pools of PI(4)P contribute to plasma membrane PI(4,5)P ₂ and maintenance of KCNQ2/3 ion channel current

Dickson

Jensen

Hille

2014

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

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Plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] regulates the activity of many ion channels and other membrane-associated proteins. To determine precursor sources of the PM PI(4,5)P 2 pool in tsA-201 cells, we monitored KCNQ2/3 channel currents and translocation of PH PLCδ1 domains as real-time indicators of PM PI(4,5)P 2 , and translocation of PH OSH2×2 , and PH OSH1 domains as indicators of PM and Golgi phosphatidylinositol 4-phosphate [PI(4)P], respectively. We selectively depleted PI(4)P pools at the PM, Golgi, or both using the rapamycin-recruitable lipid 4-phosphatases. Depleting PI(4)P at the PM with a recruitable 4-phosphatase (Sac1) results in a decrease of PI(4,5)P 2 measured by electrical or optical indicators. Depleting PI(4)P at the Golgi with the 4-phosphatase or disrupting membrane-transporting motors induces a decline in PM PI(4,5)P 2 . Depleting PI(4)P simultaneously at both the Golgi and the PM induces a larger decrease of PI(4,5)P 2 . The decline of PI(4,5)P 2 following 4-phosphatase recruitment takes 1-2 min. Recruiting the endoplasmic reticulum (ER) toward the Golgi membranes mimics the effects of depleting PI(4)P at the Golgi, apparently due to the trans actions of endogenous ER Sac1. Thus, maintenance of the PM pool of PI(4,5)P 2 appears to depend on precursor pools of PI(4)P both in the PM and in the Golgi. The decrease in PM PI(4,5)P 2 when Sac1 is recruited to the Golgi suggests that the Golgi contribution is ongoing and that PI (4,5)P 2 production may be coupled to important cell biological processes such as membrane trafficking or lipid transfer activity.phosphoinositides | wortmannin | pleckstrin homology domain T his paper concerns the dynamics of cellular pools of phosphoinositides, a family of phospholipids located on the cytoplasmic leaflet of cellular membranes, that maintain cell structure, cell motility, membrane identity, and membrane trafficking; they also play key roles in signal transduction (1). Phosphatidylinositol (PI) can be phosphorylated at three positions to generate seven additional species. The subcellular localization of each phosphoinositide is tightly governed by the concurrent presence of lipid kinases and lipid phosphatases (2, 3), giving each membrane within the cell a unique and dynamic phosphoinositide signature (4). Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] is localized to the inner leaflet of the plasma membrane (PM) and is the major substrate of phospholipase C (PLC). As a consequence, PI(4,5)P 2 levels are dynamically regulated by G q -coupled receptors activating PLC. The activity of lipid kinases and phosphatases also can be modulated by signaling; for example, a PI 4-kinase, when associated with neuronal calcium sensor-1, is accelerated in response to elevated calcium that occurs with PI(4,5)P 2 cleavage (5). In addition, transient apposition between organelles can alter phosphoinositide levels by presenting membrane-bound phosphatases in trans. For example, the endoplasmic reticulum (ER) can make contacts with the...

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Phosphatidylinositol 4-kinase is required for endosomal trafficking and degradation of the EGF receptor

Cited by 123 publications

References 34 publications

A phosphoinositide conversion mechanism for exit from endosomes

A phosphoinositide conversion mechanism for exit from endosomes

PI4KIIα is a novel regulator of tumor growth by its action on angiogenesis and HIF-1α regulation

Golgi and plasma membrane pools of PI(4)P contribute to plasma membrane PI(4,5)P ₂ and maintenance of KCNQ2/3 ion channel current

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Phosphatidylinositol 4-kinase is required for endosomal trafficking and degradation of the EGF receptor

Cited by 123 publications

References 34 publications

A phosphoinositide conversion mechanism for exit from endosomes

A phosphoinositide conversion mechanism for exit from endosomes

PI4KIIα is a novel regulator of tumor growth by its action on angiogenesis and HIF-1α regulation

Golgi and plasma membrane pools of PI(4)P contribute to plasma membrane PI(4,5)P 2 and maintenance of KCNQ2/3 ion channel current

Contact Info

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Golgi and plasma membrane pools of PI(4)P contribute to plasma membrane PI(4,5)P ₂ and maintenance of KCNQ2/3 ion channel current