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Julien Viaud - One of the best experts on this subject based on the ideXlab platform.
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Current Protocols in Protein Science - Protein-Lipid Interaction by Fluorescence (PLIF) to Characterize and Screen for Inhibitors of Protein-Phosphoinositide Interactions.
Current protocols in protein science, 2017Co-Authors: Laurie Ceccato, Frédérique Gaits-iacovoni, Mélanie Mansat, Bernard Payrastre, Julien ViaudAbstract:Phosphoinositides are key signaling and regulatory phospholipids that mediate important pathophysiological processes. This is achieved through the interaction of their phosphorylated inositol head group with a wide range of protein domains. Therefore, being able to determine the phosphoinositide specificity for effector protein is essential to the understanding of its cellular function. This unit describes a novel method named Protein-Lipid Interaction by Fluorescence, or PLIF. PLIF is a fast, reliable and high throughput assay that allows determination of the phosphoinositide specificity of proteins, simultaneously providing relative affinities. In addition, PLIF is suitable for screening inhibitors of protein- phosphoinositide interaction, allowing identification of potential pharmacological compounds. © 2017 by John Wiley & Sons, Inc.
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Phosphoinositides important lipids in the coordination of cell dynamics
Biochimie, 2016Co-Authors: Julien Viaud, Gaëtan Chicanne, Rana Mansour, Adrien Antkowiak, Abdulrahman Mujalli, Colin Valet, Jeanmarie Xuereb, Annedominique Terrisse, Sonia Severin, Mariepierre GratacapAbstract:By interacting specifically with proteins, Phosphoinositides organize the spatiotemporal formation of protein complexes involved in the control of intracellular signaling, vesicular trafficking and cytoskeleton dynamics. A set of specific kinases and phosphatases ensures the production, degradation and inter-conversion of Phosphoinositides to achieve a high level of precision in the regulation of cellular dynamics coordinated by these lipids. The direct involvement of these enzymes in cancer, genetic or infectious diseases, and the recent arrival of inhibitors targeting specific phosphoinositide kinases in clinic, emphasize the importance of these lipids and their metabolism in the biomedical field.
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PLIF: A rapid, accurate method to detect and quantitatively assess protein-lipid interactions.
Science signaling, 2016Co-Authors: Laurie Ceccato, Frédérique Gaits-iacovoni, Bernard Payrastre, Gaëtan Chicanne, Virginie Nahoum, Véronique Pons, Julien ViaudAbstract:Phosphoinositides are a type of cellular phospholipid that regulate signaling in a wide range of cellular and physiological processes through the interaction between their phosphorylated inositol head group and specific domains in various cytosolic proteins. These lipids also influence the activity of transmembrane proteins. Aberrant phosphoinositide signaling is associated with numerous diseases, including cancer, obesity, and diabetes. Thus, identifying phosphoinositide-binding partners and the aspects that define their specificity can direct drug development. However, current methods are costly, time-consuming, or technically challenging and inaccessible to many laboratories. We developed a method called PLIF (for "protein-lipid interaction by fluorescence") that uses fluorescently labeled liposomes and tethered, tagged proteins or peptides to enable fast and reliable determination of protein domain specificity for given Phosphoinositides in a membrane environment. We validated PLIF against previously known phosphoinositide-binding partners for various proteins and obtained relative affinity profiles. Moreover, PLIF analysis of the sorting nexin (SNX) family revealed not only that SNXs bound most strongly to phosphatidylinositol 3-phosphate (PtdIns3P or PI3P), which is known from analysis with other methods, but also that they interacted with other Phosphoinositides, which had not previously been detected using other techniques. Different phosphoinositide partners, even those with relatively weak binding affinity, could account for the diverse functions of SNXs in vesicular trafficking and protein sorting. Because PLIF is sensitive, semiquantitative, and performed in a high-throughput manner, it may be used to screen for highly specific protein-lipid interaction inhibitors.
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Phosphoinositides: the lipids coordinating cell dynamics
Medecine sciences : M S, 2015Co-Authors: Julien Viaud, Bernard PayrastreAbstract:Within the glycerophospholipid family, Phosphoinositides, which are minor components of eukaryotic cell membranes, play a critical role as spatiotemporal organizers of cell dynamics. By specifically interacting with proteins, they coordinate the formation and the organization of multiprotein complexes involved in cell signaling, intracellular trafficking and cytoskeleton rearrangement. The highly precise spatiotemporal dynamics of Phosphoinositides-regulated mechanisms is ensured by kinases and phosphatases that specifically produce, hydrolyze and control the interconversion of these lipids. The direct implication of these enzymes in human pathologies such as genetic diseases, cancer or infectious pathologies, and the recent arrival of inhibitors targeting some phosphoinositide kinases in clinic, illustrate the mandatory functions of these fascinating lipids.
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bin1 m amphiphysin2 induces clustering of Phosphoinositides to recruit its downstream partner dynamin
Nature Communications, 2014Co-Authors: Laura Picas, Julien Viaud, Kristine Schauer, Stefano Vanni, Karim Hnia, Vincent Fraisier, Aurelien Roux, Patricia Bassereau, Frederique Gaitsiacovoni, Bernard PayrastreAbstract:Phosphoinositides play a central role in many physiological processes by assisting the recruitment of proteins to membranes through specific phosphoinositide-binding motifs. How this recruitment is coordinated in space and time is not well understood. Here we show that BIN1/M-Amphiphysin2, a protein involved in T-tubule biogenesis in muscle cells and frequently mutated in centronuclear myopathies, clusters PtdIns(4,5)P2 to recruit its downstream partner dynamin. By using several mutants associated with centronuclear myopathies, we find that the N-BAR and the SH3 domains of BIN1 control the kinetics and the accumulation of dynamin on membranes, respectively. We show that phosphoinositide clustering is a mechanism shared by other proteins that interact with PtdIns(4,5)P2, but do not contain a BAR domain. Our numerical simulations point out that clustering is a diffusion-driven process in which phosphoinositide molecules are not sequestered. We propose that this mechanism plays a key role in the recruitment of downstream phosphoinositide-binding proteins.
Bernard Payrastre - One of the best experts on this subject based on the ideXlab platform.
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Current Protocols in Protein Science - Protein-Lipid Interaction by Fluorescence (PLIF) to Characterize and Screen for Inhibitors of Protein-Phosphoinositide Interactions.
Current protocols in protein science, 2017Co-Authors: Laurie Ceccato, Frédérique Gaits-iacovoni, Mélanie Mansat, Bernard Payrastre, Julien ViaudAbstract:Phosphoinositides are key signaling and regulatory phospholipids that mediate important pathophysiological processes. This is achieved through the interaction of their phosphorylated inositol head group with a wide range of protein domains. Therefore, being able to determine the phosphoinositide specificity for effector protein is essential to the understanding of its cellular function. This unit describes a novel method named Protein-Lipid Interaction by Fluorescence, or PLIF. PLIF is a fast, reliable and high throughput assay that allows determination of the phosphoinositide specificity of proteins, simultaneously providing relative affinities. In addition, PLIF is suitable for screening inhibitors of protein- phosphoinositide interaction, allowing identification of potential pharmacological compounds. © 2017 by John Wiley & Sons, Inc.
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PLIF: A rapid, accurate method to detect and quantitatively assess protein-lipid interactions.
Science signaling, 2016Co-Authors: Laurie Ceccato, Frédérique Gaits-iacovoni, Bernard Payrastre, Gaëtan Chicanne, Virginie Nahoum, Véronique Pons, Julien ViaudAbstract:Phosphoinositides are a type of cellular phospholipid that regulate signaling in a wide range of cellular and physiological processes through the interaction between their phosphorylated inositol head group and specific domains in various cytosolic proteins. These lipids also influence the activity of transmembrane proteins. Aberrant phosphoinositide signaling is associated with numerous diseases, including cancer, obesity, and diabetes. Thus, identifying phosphoinositide-binding partners and the aspects that define their specificity can direct drug development. However, current methods are costly, time-consuming, or technically challenging and inaccessible to many laboratories. We developed a method called PLIF (for "protein-lipid interaction by fluorescence") that uses fluorescently labeled liposomes and tethered, tagged proteins or peptides to enable fast and reliable determination of protein domain specificity for given Phosphoinositides in a membrane environment. We validated PLIF against previously known phosphoinositide-binding partners for various proteins and obtained relative affinity profiles. Moreover, PLIF analysis of the sorting nexin (SNX) family revealed not only that SNXs bound most strongly to phosphatidylinositol 3-phosphate (PtdIns3P or PI3P), which is known from analysis with other methods, but also that they interacted with other Phosphoinositides, which had not previously been detected using other techniques. Different phosphoinositide partners, even those with relatively weak binding affinity, could account for the diverse functions of SNXs in vesicular trafficking and protein sorting. Because PLIF is sensitive, semiquantitative, and performed in a high-throughput manner, it may be used to screen for highly specific protein-lipid interaction inhibitors.
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Phosphoinositides: the lipids coordinating cell dynamics
Medecine sciences : M S, 2015Co-Authors: Julien Viaud, Bernard PayrastreAbstract:Within the glycerophospholipid family, Phosphoinositides, which are minor components of eukaryotic cell membranes, play a critical role as spatiotemporal organizers of cell dynamics. By specifically interacting with proteins, they coordinate the formation and the organization of multiprotein complexes involved in cell signaling, intracellular trafficking and cytoskeleton rearrangement. The highly precise spatiotemporal dynamics of Phosphoinositides-regulated mechanisms is ensured by kinases and phosphatases that specifically produce, hydrolyze and control the interconversion of these lipids. The direct implication of these enzymes in human pathologies such as genetic diseases, cancer or infectious pathologies, and the recent arrival of inhibitors targeting some phosphoinositide kinases in clinic, illustrate the mandatory functions of these fascinating lipids.
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bin1 m amphiphysin2 induces clustering of Phosphoinositides to recruit its downstream partner dynamin
Nature Communications, 2014Co-Authors: Laura Picas, Julien Viaud, Kristine Schauer, Stefano Vanni, Karim Hnia, Vincent Fraisier, Aurelien Roux, Patricia Bassereau, Frederique Gaitsiacovoni, Bernard PayrastreAbstract:Phosphoinositides play a central role in many physiological processes by assisting the recruitment of proteins to membranes through specific phosphoinositide-binding motifs. How this recruitment is coordinated in space and time is not well understood. Here we show that BIN1/M-Amphiphysin2, a protein involved in T-tubule biogenesis in muscle cells and frequently mutated in centronuclear myopathies, clusters PtdIns(4,5)P2 to recruit its downstream partner dynamin. By using several mutants associated with centronuclear myopathies, we find that the N-BAR and the SH3 domains of BIN1 control the kinetics and the accumulation of dynamin on membranes, respectively. We show that phosphoinositide clustering is a mechanism shared by other proteins that interact with PtdIns(4,5)P2, but do not contain a BAR domain. Our numerical simulations point out that clustering is a diffusion-driven process in which phosphoinositide molecules are not sequestered. We propose that this mechanism plays a key role in the recruitment of downstream phosphoinositide-binding proteins.
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BIN1/M-Amphiphysin2 induces clustering of Phosphoinositides to recruit its downstream partner dynamin
Nature Communications, 2014Co-Authors: Laura Picas, Frédérique Gaits-iacovoni, Julien Viaud, Kristine Schauer, Stefano Vanni, Karim Hnia, Vincent Fraisier, Aurelien Roux, Patricia Bassereau, Bernard PayrastreAbstract:Phosphoinositides play a central role in many physiological processes by assisting the recruitment of proteins to membranes through specific phosphoinositide-binding motifs. How this recruitment is coordinated in space and time is not well understood. Here we show that BIN1/M-Amphiphysin2, a protein involved in T-tubule biogenesis in muscle cells and frequently mutated in centronuclear myopathies, clusters PtdIns(4,5)P2 to recruit its downstream partner dynamin. By using several mutants associated with centronuclear myopathies, we find that the N-BAR and the SH3 domains of BIN1 control the kinetics and the accumulation of dynamin on membranes, respectively. We show that phosphoinositide clustering is a mechanism shared by other proteins that interact with PtdIns(4,5)P2, but do not contain a BAR domain. Our numerical simulations point out that clustering is a diffusion-driven process in which phosphoinositide molecules are not sequestered. We propose that this mechanism plays a key role in the recruitment of downstream phosphoinositide-binding proteins.
Frédérique Gaits-iacovoni - One of the best experts on this subject based on the ideXlab platform.
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Current Protocols in Protein Science - Protein-Lipid Interaction by Fluorescence (PLIF) to Characterize and Screen for Inhibitors of Protein-Phosphoinositide Interactions.
Current protocols in protein science, 2017Co-Authors: Laurie Ceccato, Frédérique Gaits-iacovoni, Mélanie Mansat, Bernard Payrastre, Julien ViaudAbstract:Phosphoinositides are key signaling and regulatory phospholipids that mediate important pathophysiological processes. This is achieved through the interaction of their phosphorylated inositol head group with a wide range of protein domains. Therefore, being able to determine the phosphoinositide specificity for effector protein is essential to the understanding of its cellular function. This unit describes a novel method named Protein-Lipid Interaction by Fluorescence, or PLIF. PLIF is a fast, reliable and high throughput assay that allows determination of the phosphoinositide specificity of proteins, simultaneously providing relative affinities. In addition, PLIF is suitable for screening inhibitors of protein- phosphoinositide interaction, allowing identification of potential pharmacological compounds. © 2017 by John Wiley & Sons, Inc.
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The emerging role of phosphoinositide clustering in intracellular trafficking and signal transduction.
F1000Research, 2016Co-Authors: Laura Picas, Frédérique Gaits-iacovoni, Bruno GoudAbstract:Phosphoinositides are master regulators of multiple cellular processes: from vesicular trafficking to signaling, cytoskeleton dynamics, and cell growth. They are synthesized by the spatiotemporal regulated activity of phosphoinositide-metabolizing enzymes. The recent observation that some protein modules are able to cluster Phosphoinositides suggests that alternative or complementary mechanisms might operate to stabilize the different phosphoinositide pools within cellular compartments. Herein, we discuss the different known and potential molecular players that are prone to engage phosphoinositide clustering and elaborate on how such a mechanism might take part in the regulation of intracellular trafficking and signal transduction.
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PLIF: A rapid, accurate method to detect and quantitatively assess protein-lipid interactions.
Science signaling, 2016Co-Authors: Laurie Ceccato, Frédérique Gaits-iacovoni, Bernard Payrastre, Gaëtan Chicanne, Virginie Nahoum, Véronique Pons, Julien ViaudAbstract:Phosphoinositides are a type of cellular phospholipid that regulate signaling in a wide range of cellular and physiological processes through the interaction between their phosphorylated inositol head group and specific domains in various cytosolic proteins. These lipids also influence the activity of transmembrane proteins. Aberrant phosphoinositide signaling is associated with numerous diseases, including cancer, obesity, and diabetes. Thus, identifying phosphoinositide-binding partners and the aspects that define their specificity can direct drug development. However, current methods are costly, time-consuming, or technically challenging and inaccessible to many laboratories. We developed a method called PLIF (for "protein-lipid interaction by fluorescence") that uses fluorescently labeled liposomes and tethered, tagged proteins or peptides to enable fast and reliable determination of protein domain specificity for given Phosphoinositides in a membrane environment. We validated PLIF against previously known phosphoinositide-binding partners for various proteins and obtained relative affinity profiles. Moreover, PLIF analysis of the sorting nexin (SNX) family revealed not only that SNXs bound most strongly to phosphatidylinositol 3-phosphate (PtdIns3P or PI3P), which is known from analysis with other methods, but also that they interacted with other Phosphoinositides, which had not previously been detected using other techniques. Different phosphoinositide partners, even those with relatively weak binding affinity, could account for the diverse functions of SNXs in vesicular trafficking and protein sorting. Because PLIF is sensitive, semiquantitative, and performed in a high-throughput manner, it may be used to screen for highly specific protein-lipid interaction inhibitors.
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BIN1/M-Amphiphysin2 induces clustering of Phosphoinositides to recruit its downstream partner dynamin
Nature Communications, 2014Co-Authors: Laura Picas, Frédérique Gaits-iacovoni, Julien Viaud, Kristine Schauer, Stefano Vanni, Karim Hnia, Vincent Fraisier, Aurelien Roux, Patricia Bassereau, Bernard PayrastreAbstract:Phosphoinositides play a central role in many physiological processes by assisting the recruitment of proteins to membranes through specific phosphoinositide-binding motifs. How this recruitment is coordinated in space and time is not well understood. Here we show that BIN1/M-Amphiphysin2, a protein involved in T-tubule biogenesis in muscle cells and frequently mutated in centronuclear myopathies, clusters PtdIns(4,5)P2 to recruit its downstream partner dynamin. By using several mutants associated with centronuclear myopathies, we find that the N-BAR and the SH3 domains of BIN1 control the kinetics and the accumulation of dynamin on membranes, respectively. We show that phosphoinositide clustering is a mechanism shared by other proteins that interact with PtdIns(4,5)P2, but do not contain a BAR domain. Our numerical simulations point out that clustering is a diffusion-driven process in which phosphoinositide molecules are not sequestered. We propose that this mechanism plays a key role in the recruitment of downstream phosphoinositide-binding proteins.
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Phosphoinositides and cellular pathogens.
Sub-cellular biochemistry, 2012Co-Authors: Bernard Payrastre, Frédérique Gaits-iacovoni, Philippe J. Sansonetti, Hélène TronchèreAbstract:Phosphoinositides are considered as highly dynamic players in the spatiotemporal organization of key signaling pathways, actin cytoskeleton rearrangements, establishment of cell polarity and intracellular vesicle trafficking. Their metabolism is accurately controlled and mutations in several phosphoinositide metabolizing enzymes take part in the development of human pathologies. Interestingly, evidence is accumulating that modulation of the phosphoinositide metabolism is critical for pathogenicity and virulence of many human pathogens. Given the importance of Phosphoinositides, which link membrane and cytoskeleton dynamics to cell responses, it is not surprising that many invasive pathogens hijack their metabolism as part of their strategies to establish infection. In fact, according to their lifestyle, cellular pathogens use the phosphoinositide metabolism in order to trigger their uptake in nonphagocytic cells and/or modulate the maturation of the pathogen-containing vacuole to establish their replicative niche or escape in the cytosol and promote host cell survival. The last two decades have been marked by the discovery of different tactics used by cellular pathogens to modulate the phosphoinositide metabolism as part of their strategies to survive, proliferate and disseminate in a hostile environment.
Bart Vanhaesebroeck - One of the best experts on this subject based on the ideXlab platform.
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Phosphoinositide lipids in primary cilia biology.
The Biochemical journal, 2020Co-Authors: Sarah E. Conduit, Bart VanhaesebroeckAbstract:Primary cilia are solitary signalling organelles projecting from the surface of most cell types. Although the ciliary membrane is continuous with the plasma membrane it exhibits a unique phospholipid composition, a feature essential for normal cilia formation and function. Recent studies have illustrated that distinct phosphoinositide lipid species localise to specific cilia subdomains, and have begun to build a 'phosphoinositide map' of the cilium. The abundance and localisation of Phosphoinositides are tightly regulated by the opposing actions of lipid kinases and lipid phosphatases that have also been recently discovered at cilia. The critical role of Phosphoinositides in cilia biology is highlighted by the devastating consequences of genetic defects in cilia-associated phosphoinositide regulatory enzymes leading to ciliopathy phenotypes in humans and experimental mouse and zebrafish models. Here we provide a general introduction to primary cilia and the roles Phosphoinositides play in cilia biology. In addition to increasing our understanding of fundamental cilia biology, this rapidly expanding field may inform novel approaches to treat ciliopathy syndromes caused by deregulated phosphoinositide metabolism.
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Signalling through phosphoinositide 3-kinases: the lipids take centre stage.
Current opinion in cell biology, 1999Co-Authors: Sally J. Leevers, Bart Vanhaesebroeck, Michael D. WaterfieldAbstract:Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids at the 3' position of the inositol ring to generate the 3-Phosphoinositides PI(3)P, PI(3,4) P2 and PI(3,4,5) P3. Recent research has shown that one way in which these lipids function in signal transduction and membrane trafficking is by interacting with 3-phosphoinositide-binding modules in a broad variety of proteins. Specifically, certain FYVE domains bind PI(3)P whereas certain pleckstrin homology domains bind PI(3,4) P2 and/or PI(3,4,5) P3. Also in 1998, PTEN - a major tumour suppressor in human cancer - was also shown to antagonise PI3K signalling by removing the 3-phosphate from 3-Phosphoinositides.
Pascale Cossart - One of the best experts on this subject based on the ideXlab platform.
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Phosphoinositides and host-pathogen interactions.
BBA - Biochimica et Biophysica Acta, 2015Co-Authors: Javier Pizarro-cerdá, Andreas Kühbacher, Pascale CossartAbstract:Phosphoinositides control key cellular processes including vesicular trafficking and actin polymerization. Intracellular bacterial pathogens manipulate phosphoinositide metabolism in order to promote their uptake by target cells and to direct in some cases the biogenesis of their replication compartments. In this chapter, we review the molecular strategies that major pathogens including Listeria, Mycobacterium, Shigella, Salmonella, Legionella and Yersinia use to hijack Phosphoinositides during infection. This article is part of a Special Issue entitled Phosphoinositides.
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Phosphoinositides and host–pathogen interactions
Biochimica et biophysica acta, 2014Co-Authors: Javier Pizarro-cerdá, Andreas Kühbacher, Pascale CossartAbstract:Phosphoinositides control key cellular processes including vesicular trafficking and actin polymerization. Intracellular bacterial pathogens manipulate phosphoinositide metabolism in order to promote their uptake by target cells and to direct in some cases the biogenesis of their replication compartments. In this chapter, we review the molecular strategies that major pathogens including Listeria, Mycobacterium, Shigella, Salmonella, Legionella and Yersinia use to hijack Phosphoinositides during infection. This article is part of a Special Issue entitled Phosphoinositides.
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Subversion of phosphoinositide metabolism by intracellular bacterial pathogens
Nature Cell Biology, 2004Co-Authors: Javier Pizzaro-cerda, Pascale CossartAbstract:Phosphoinositides are short-lived lipids, whose production at specific membrane locations in the cell enables the tightly controlled recruitment or activation of diverse cellular effectors involved in processes such as cell motility or phagocytosis. Bacterial pathogens have evolved molecular mechanisms to subvert phosphoinositide metabolism in host cells, promoting (or blocking) their internalization into target tissues, and/or modifying the maturation fate of their proliferating compartments within the intracellular environment.