Phosphatidylinositol 5-phosphate is a second messenger important for cell migration

Haugsten, Ellen Margrethe; Oppelt, Angela; Wesche, Jørgen

doi:10.4161/cib.25446

Cited by 10 publications

(10 citation statements)

References 18 publications

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“…In line with these observations, recent studies have identified PtdIns5P as the central molecule regulating cell migration in response to FGF1 in fibroblasts and border cells during Drosophila embryogenesis . These studies revealed that PIKfyve and MTMR3 act together to produce PtdIns(3,5)P 2 and its metabolite PtdIns5P.…”

Section: Ptdins5p In the Plasma Membrane And Intracellular Membranessupporting

confidence: 53%

Phosphatidylinositol 5‐phosphate: A nuclear stress lipid and a tuner of membranes and cytoskeleton dynamics

et al. 2013

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Phosphatidylinositol 5-phosphate (PtdIns5P), the least characterized among the three phosphatidylinositol monophosphates, is emerging as a bioactive lipid involved in the control of several cellular functions. Similar to PtdIns3P, it is present in low amounts in mammalian cells, and can be detected at the plasma membrane and endomembranes as well as in the nucleus. Changes in PtdIns5P levels are observed in mammalian cells following specific stimuli or stresses, and in human diseases. Recently, the contribution of several enzymes such as PIKfyve, myotubularins, and type II PtdInsP-kinases to PtdIns5P metabolism has gained a strong experimental support. Here, we provide a picture emerging from recent studies showing how this lipid can be generated and act as a regulator of membrane and cytoskeleton dynamics, and as a modulator of gene expression. We briefly summarize the current methods and tools for studying PtdIns5P, and discuss how PtdIns5P can integrate and coordinate different functions in a spatiotemporal manner.

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Section: Ptdins5p In the Plasma Membrane And Intracellular Membranessupporting

confidence: 53%

Phosphatidylinositol 5‐phosphate: A nuclear stress lipid and a tuner of membranes and cytoskeleton dynamics

et al. 2013

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“…It was recently shown that FGF-1 stimulated 2D migration of BJ foreskin fibroblasts by producing PtdIns5P through a signalling cascade that involved the class III PI 3-kinase Vps34, PIKfyve and the MTMR3 myotubularin 15,27 . We therefore checked whether PtdIns5P was a feature of FGF-1 stimulation by measuring PtdIns5P production in RPE-1 cells.…”

Section: Resultsmentioning

confidence: 99%

Phosphatidylinositol 5-phosphate regulates invasion through binding and activation of Tiam1

et al. 2014

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PtdIns5P is a lipid messenger acting as a stress-response mediator in the nucleus, and known to maintain cell activation through traffic alterations upon bacterial infection. Here, we show that PtdIns5P regulates actin dynamics and invasion via recruitment and activation of the exchange factor Tiam1 and Rac1. Restricted Rac1 activation results from the binding of Tiam1 DH-PH domains to PtdIns5P. Using an assay that mimics Rac1 membrane anchoring by using Rac1-His and liposomes containing Ni 2 þ -NTA modified lipids, we demonstrate that intrinsic Tiam1 DH-PH activity increases when Rac1 is anchored in a PtdIns5P-enriched environment. This pathway appears to be general since it is valid in different pathophysiological models: receptor tyrosine kinase activation, bacterial phosphatase IpgD expression and the invasive NPM-ALK( þ ) lymphomas. The discovery that PtdIns5P could be a keystone of GTPases and cytoskeleton spatiotemporal regulation opens important research avenues towards unravelling new strategies counteracting cell invasion.

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“…The Golgi complex, in particular the TGN, is characterized by PI(4)P, a PI that is of particular importance for the integrity of the Golgi, largely through its involvement in AP-1-and GGA-dependent vesicle formation at the TGN (Wang, Sun et al 2007). So far, the subcellular distribution of PI(5)P remains poorly understood, although a regulatory role in autophagosome biogenesis (Vicinanza, Korolchuk et al 2015), cell migration and enzymatic activity of PI(3,5)P 2 -metabolizing enzymes was reported (Haugsten, Oppelt et al 2013;Oppelt, Lobert et al 2013).…”

Section: Phosphoinositides Serve As Spatio-temporal Landmarksmentioning

confidence: 99%

A phosphoinositide conversion mechanism for exit from endosomes

Ketel¹,

Krauß²,

Nicot³

et al. 2016

Nature

161

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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Phosphatidylinositol 5-phosphate is a second messenger important for cell migration

Cited by 10 publications

References 18 publications

Phosphatidylinositol 5‐phosphate: A nuclear stress lipid and a tuner of membranes and cytoskeleton dynamics

Phosphatidylinositol 5‐phosphate: A nuclear stress lipid and a tuner of membranes and cytoskeleton dynamics

Phosphatidylinositol 5-phosphate regulates invasion through binding and activation of Tiam1

A phosphoinositide conversion mechanism for exit from endosomes

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