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19 results on '"Mohyeddine Omrane"'

1. Giant organelle vesicles to uncover intracellular membrane mechanics and plasticity

Author

Alexandre Santinho, Maxime Carpentier, Julio Lopes Sampaio, Mohyeddine Omrane, and Abdou Rachid Thiam

Subjects
Science
Abstract

Abstract Tools for accessing and studying organelles remain underdeveloped. Here, we present a method by which giant organelle vesicles (GOVs) are generated by submitting cells to a hypotonic medium followed by plasma membrane breakage. By this means, GOVs ranging from 3 to over 10 µm become available for micromanipulation. GOVs are made from organelles such as the endoplasmic reticulum, endosomes, lysosomes and mitochondria, or in contact with one another such as giant mitochondria-associated ER membrane vesicles. We measure the mechanical properties of each organelle-derived GOV and find that they have distinct properties. In GOVs procured from Cos7 cells, for example, bending rigidities tend to increase from the endoplasmic reticulum to the plasma membrane. We also found that the mechanical properties of giant endoplasmic reticulum vesicles (GERVs) vary depending on their interactions with other organelles or the metabolic state of the cell. Lastly, we demonstrate GERVs’ biochemical activity through their capacity to synthesize triglycerides and assemble lipid droplets. These findings underscore the potential of GOVs as valuable tools for studying the biophysics and biology of organelles.

Published
2024
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3. Perilipin membrane integration determines lipid droplet heterogeneity in differentiating adipocytes

Author

Mario Majchrzak, Ozren Stojanović, Dalila Ajjaji, Kalthoum Ben M’barek, Mohyeddine Omrane, Abdou Rachid Thiam, and Robin W. Klemm

Subjects
CP: Cell biology, CP: Metabolism, Biology (General), QH301-705.5
Abstract

Summary: The storage of fat within lipid droplets (LDs) of adipocytes is critical for whole-body health. Acute fatty acid (FA) uptake by differentiating adipocytes leads to the formation of at least two LD classes marked by distinct perilipins (PLINs). How this LD heterogeneity arises is an important yet unresolved cell biological problem. Here, we show that an unconventional integral membrane segment (iMS) targets the adipocyte specific LD surface factor PLIN1 to the endoplasmic reticulum (ER) and facilitates high-affinity binding to the first LD class. The other PLINs remain largely excluded from these LDs until FA influx recruits them to a second LD population. Preventing ER targeting turns PLIN1 into a soluble, cytoplasmic LD protein, reduces its LD affinity, and switches its LD class specificity. Conversely, moving the iMS to PLIN2 leads to ER insertion and formation of a separate LD class. Our results shed light on how differences in organelle targeting and disparities in lipid affinity of LD surface factors contribute to formation of LD heterogeneity.

Published
2024
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4. Cholesterol esters form supercooled lipid droplets whose nucleation is facilitated by triacylglycerols

Author

Calvin Dumesnil, Lauri Vanharanta, Xavier Prasanna, Mohyeddine Omrane, Maxime Carpentier, Apoorva Bhapkar, Giray Enkavi, Veijo T. Salo, Ilpo Vattulainen, Elina Ikonen, and Abdou Rachid Thiam

Subjects
Science
Abstract

Dumesnil et al. report that cholesterol esters (CE), which only melt above body temperature, form supercooled liquid crystalline lipid droplets (LD). Triacylglycerols (TG) solubilize CE to help CE LD nucleation. Through clustering TGs in the ER membrane, seipin controls CE LD nucleation sites.

Published
2023
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5. ARL8B mediates lipid droplet contact and delivery to lysosomes for lipid remobilization

Author

Dilip Menon, Apoorva Bhapkar, Bhoomika Manchandia, Gitanjali Charak, Surabhi Rathore, Rakesh Mohan Jha, Arpita Nahak, Moumita Mondal, Mohyeddine Omrane, Akash Kumar Bhaskar, Lipi Thukral, Abdou Rachid Thiam, and Sheetal Gandotra

Subjects
CP: Cell biology, CP: Immunology, Biology (General), QH301-705.5
Abstract

Summary: Lipid droplets (LDs) play a crucial role in maintaining cellular lipid balance by storing and delivering lipids as needed. However, the intricate lipolytic pathways involved in LD turnover remain poorly described, hindering our comprehension of lipid catabolism and related disorders. Here, we show a function of the small GTPase ARL8B in mediating LD turnover in lysosomes. ARL8B-GDP localizes to LDs, while ARL8-GTP predominantly favors lysosomes. GDP binding induces a conformation with an exposed N-terminal amphipathic helix, enabling ARL8B to bind to LDs. By associating with LDs and lysosomes, and with its property to form a heterotypic complex, ARL8B mediates LD-lysosome contacts and efficient lipid transfer between these organelles. In human macrophages, this ARL8B-dependent LD turnover mechanism appears as the major lipolytic pathway. Our finding opens exciting possibilities for understanding the molecular mechanisms underlying LD degradation and its potential implications for inflammatory disorders.

Published
2023
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6. Septin 9 Orients the Apico–Basal Polarity Axis and Controls Plasticity Signals

Author

Tingting Cai, Juan Peng, Mohyeddine Omrane, Nassima Benzoubir, Didier Samuel, and Ama Gassama-Diagne

Subjects
septin 9, apico–basal polarity, polybasic domains, TGFβ/RhoA, Cytology, QH573-671
Abstract

The cytoskeleton is a master organizer of the cellular cortex and membrane trafficking and therefore plays a crucial role in apico–basal polarity. Septins form a family of GTPases that assemble into non-polar filaments, which bind to membranes and recruit cytoskeletal elements such as microtubules and actin using their polybasic (PB) domains, to perform their broad biological functions. Nevertheless, the role of septins and the significance of their membrane-binding ability in apico–basal polarity remains under-investigated. Here, using 3D cultures, we demonstrated that septin 9 localizes to the basolateral membrane (BM). Its depletion induces an inverted polarity phenotype, decreasing β-catenin at BM and increasing transforming growth factor (TGFβ) and Epithelial–Mesenchymal Transition (EMT) markers. Similar effects were observed after deleting its two PB domains. The mutant became cytoplasmic and apical. The cysts with an inverted polarity phenotype displayed an invasive phenotype, with src and cortactin accumulating at the peripheral membrane. The inhibition of TGFβ-receptor and RhoA rescued the polarized phenotype, although the cysts from overexpressed septin 9 overgrew and presented a filled lumen. Both phenotypes corresponded to tumor features. This suggests that septin 9 expression, along with its assembly through the two PB domains, is essential for establishing and maintaining apico–basal polarity against tumor development.

Published
2023
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7. Triacylglycerols sequester monotopic membrane proteins to lipid droplets

Author

Lucie Caillon, Vincent Nieto, Pauline Gehan, Mohyeddine Omrane, Nicolas Rodriguez, Luca Monticelli, and Abdou Rachid Thiam

Subjects
Science
Abstract

Triacylglycerols (TG) are synthesized at the endoplasmic reticulum (ER) bilayer and packaged into monolayer lipid droplets (LDs), but how proteins partition between ER and LDs is poorly understood. Here authors use synthetic model systems and find that proteins containing hydrophobic membrane association domains strongly prefer monolayers and that returning to the bilayer is unfavorable.

Published
2020
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8. Septin 9 and phosphoinositides regulate lysosome localization and their association with lipid droplets

Author

Pei Xuan Song, Juan Peng, Mohyeddine Omrane, Ting ting Cai, Didier Samuel, and Ama Gassama-Diagne

Subjects
Cell biology, Organizational aspects of cell biology, Functional aspects of cell biology, Science
Abstract

Summary: The accumulation of lipid droplets (LDs) in the liver is a hallmark of steatosis, which is often associated with lysosomal dysfunction. Nevertheless, the underlying mechanisms remain unclear. Here, using Huh7 cells loaded with oleate as a model to study LD metabolism, we show that cellular content and distribution of LDs are correlated with those of the lysosome and regulated by oleate and septin 9. High expression of septin 9 promotes perinuclear clustering of lysosomes which co-localized with Golgi and not with their surrounding LDs. On the other hand, knockdown of septin 9 disperses the two organelles which colocalize at the cell periphery. The Rab7 is present around these peripheral LDs. PtdIns5P which binds septin 9 and MTMR3 which converts PtdIns(3,5)P2 into PtdIns(5) recapitulates the effects of septin 9. By contrast, PtdIns(3,5)P2 promotes LD/lysosome co-localization. Overall, our data reveal a phosphoinositide/septin 9-dependent mechanism that regulates LD behavior through the control of their association with lysosomes.

Published
2022
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9. Septin 9 has Two Polybasic Domains Critical to Septin Filament Assembly and Golgi Integrity

Author

Mohyeddine Omrane, Amanda Souza Camara, Cyntia Taveneau, Nassima Benzoubir, Thibault Tubiana, Jinchao Yu, Raphaël Guérois, Didier Samuel, Bruno Goud, Christian Poüs, Stéphane Bressanelli, Richard Charles Garratt, Abdou Rachid Thiam, and Ama Gassama-Diagne

Subjects
Science
Abstract

Summary: Septins are GTP-binding proteins involved in several membrane remodeling mechanisms. They associate with membranes, presumably using a polybasic domain (PB1) that interacts with phosphoinositides (PIs). Membrane-bound septins assemble into microscopic structures that regulate membrane shape. How septins interact with PIs and then assemble and shape membranes is poorly understood. Here, we found that septin 9 has a second polybasic domain (PB2) conserved in the human septin family. Similar to PB1, PB2 binds specifically to PIs, and both domains are critical for septin filament formation. However, septin 9 membrane association is not dependent on these PB domains, but on putative PB-adjacent amphipathic helices. The presence of PB domains guarantees protein enrichment in PI-contained membranes, which is critical for PI-enriched organelles. In particular, we found that septin 9 PB domains control the assembly and functionality of the Golgi apparatus. Our findings offer further insight into the role of septins in organelle morphology. : Membrane Architecture; Molecular Interaction; Cell Biology; Functional Aspects of Cell Biology Subject Areas: Membrane Architecture, Molecular Interaction, Cell Biology, Functional Aspects of Cell Biology

Published
2019
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11. Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV

Author

Abdellah Akil, Juan Peng, Mohyeddine Omrane, Claire Gondeau, Christophe Desterke, Mickaël Marin, Hélène Tronchère, Cyntia Taveneau, Sokhavuth Sar, Philippe Briolotti, Soumaya Benjelloun, Abdelaziz Benjouad, Patrick Maurel, Valérie Thiers, Stéphane Bressanelli, Didier Samuel, Christian Bréchot, and Ama Gassama-Diagne

Subjects
Science
Abstract

The accumulation of lipid droplets is often observed in hepatitis C virus infection, but the mechanism of their formation is not known. Here the authors show that septin 9 expression is increased in infected livers, and a septin 9/phosphatidylinositol 5-phosphate signalling pathway regulates the growth of lipid droplets.

Published
2016
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12. Hepatitis C virus core protein uses triacylglycerols to fold onto the endoplasmic reticulum membrane

Author

Elise Diaz, François Penin, Dalila Ajjaji, François-Loïc Cosset, Kalthoum Ben M'barek, Bertrand Ducos, Bertrand Boson, Ama Gassama-Diagne, Mohyeddine Omrane, Magali Blaud, and Abdou Rachid Thiam

Subjects
Hepacivirus, Biology, Endoplasmic Reticulum, Biochemistry, 03 medical and health sciences, Structural Biology, Lipid droplet, Genetics, Humans, Molecular Biology, Triglycerides, 030304 developmental biology, Diacylglycerol kinase, 0303 health sciences, Viral Core Proteins, Bilayer, Endoplasmic reticulum, 030302 biochemistry & molecular biology, Lipid Droplets, Cell Biology, COPI, Hepatitis C, 3. Good health, Cell biology, Capsid, Protein folding, Alpha helix
Abstract

Lipid droplets (LDs) are involved in viral infections, but exactly how remains unclear. Here, we study the hepatitis C virus (HCV) whose core capsid protein binds to LDs but is also involved in the assembly of virions at the endoplasmic reticulum (ER) bilayer. We found that the amphipathic helix-containing domain of core, D2, senses triglycerides (TGs) rather than LDs per se. In the absence of LDs, D2 can bind to the ER membrane but only if TG molecules are present in the bilayer. Accordingly, the pharmacological inhibition of the diacylglycerol O-acyltransferase enzymes, mediating TG synthesis in the ER, inhibits D2 association with the bilayer. We found that TG molecules enable D2 to fold into alpha helices. Sequence analysis reveals that D2 resembles the apoE lipid-binding region. Our data support that TG in LDs promotes the folding of core, which subsequently relocalizes to contiguous ER regions. During this motion, core may carry TG molecules to these regions where HCV lipoviroparticles likely assemble. Consistent with this model, the inhibition of Arf1/COPI, which decreases LD surface accessibility to proteins and ER-LD material exchange, severely impedes the assembly of virions. Altogether, our data uncover a critical function of TG in the folding of core and HCV replication and reveals, more broadly, how TG accumulation in the ER may provoke the binding of soluble amphipathic helix-containing proteins to the ER bilayer.

Published
2021
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13. ORP5 AND ORP8 ORCHESTRATE LIPID DROPLET BIOGENESIS AND MAINTENANCE AT ER-MITOCHONDRIA CONTACT SITES

Author

Audrey Houcine, Nicolas Vitale, Abdou Rachid Thiam, Mohyeddine Omrane, Naima El Khallouki, Francesca Giordano, Valentin Guyard, Vera F. Monteiro-Cardoso, Cécile Sauvanet, Orestis Facklaris, Claire Boulogne, Kalthoum Ben M'barek, Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Sorbonne Université (SU), Laboratoire de physique de l'ENS - ENS Paris (LPENS (UMR_8023)), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Département Plateforme (PF I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Animaux Modèles Aquatiques : ingéniérie GENétique (AMAGEN), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique de l'ENS - ENS Paris (LPENS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), and Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris)

Subjects
0303 health sciences, Receptors, Steroid, Endoplasmic reticulum, [SDV]Life Sciences [q-bio], Cell Biology, Phosphatidic acid, Lipid Droplets, Mitochondrion, Endoplasmic Reticulum, Lipid Metabolism, Seipin, Cell biology, Mitochondria, 03 medical and health sciences, chemistry.chemical_compound, Crosstalk (biology), 0302 clinical medicine, chemistry, Lipid droplet, Organelle, 030217 neurology & neurosurgery, Biogenesis, Phospholipids, 030304 developmental biology
Abstract

SUMMARYLipid droplets (LDs) are the primary organelles of lipid storage, buffering energy fluctuations of the cell. They store neutral lipids in their core that is surrounded by a protein-decorated phospholipid monolayer. LDs arise from the Endoplasmic Reticulum (ER). The ER-protein seipin, localizing at ER-LD junctions, controls LD nucleation and growth. However, how LD biogenesis is spatially and temporally coordinated remains elusive. Here, we show that the lipid transfer proteins ORP5 and ORP8 control LD biogenesis at Mitochondria-Associated ER Membrane (MAM) subdomains, enriched in phosphatidic acid. We found that ORP5/8 regulate seipin recruitment to these MAM-LD contacts, and their loss impairs LD biogenesis. Importantly, the integrity of ER-mitochondria contact sites is crucial for the ORP5/8 function in regulating seipin-mediated LD biogenesis. Our study uncovers an unprecedented ORP5/8 role in orchestrating LD biogenesis at MAMs and brings novel insights into the metabolic crosstalk between mitochondria, ER, and LDs at membrane contact sites.HIGHLIGHTSORP5 and ORP8 localize at MAM subdomains where LDs originate.Phosphatidic acid is enriched in MAM subdomains that are the birthplace of LDs.ORP5 and ORP8 knockdown impairs LD biogenesis.ORP5 and ORP8 regulate seipin recruitment to MAM-LD contact sites.

Published
2021

14. Triacylglycerols sequester monotopic membrane proteins to lipid droplets

Author

Nicolas Rodriguez, Mohyeddine Omrane, Vincent Nieto, Abdou Rachid Thiam, Lucie Caillon, Luca Monticelli, Pauline Gehan, Laboratoire de physique de l'ENS - ENS Paris (LPENS (UMR_8023)), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Microfluidique, Émulsion et Biologie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris), Gestionnaire, Hal Sorbonne Université, Laboratoire de physique de l'ENS - ENS Paris (LPENS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris)

Subjects
Science, [SDV]Life Sciences [q-bio], Lipid Bilayers, Phospholipid, General Physics and Astronomy, Molecular Dynamics Simulation, Endoplasmic Reticulum, Article, General Biochemistry, Genetics and Molecular Biology, Membrane biophysics, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Protein Domains, Lipid droplet, Monolayer, lcsh:Science, Integral membrane protein, Triglycerides, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Chemistry, Circular Dichroism, Endoplasmic reticulum, Bilayer, Cell Membrane, Membrane Proteins, Lipid Droplets, General Chemistry, [SDV] Life Sciences [q-bio], Protein Transport, Membrane protein, Biophysics, lcsh:Q, Biological physics, 030217 neurology & neurosurgery
Abstract

Triacylglycerols (TG) are synthesized at the endoplasmic reticulum (ER) bilayer and packaged into organelles called lipid droplets (LDs). LDs are covered by a single phospholipid monolayer contiguous with the ER bilayer. This connection is used by several monotopic integral membrane proteins, with hydrophobic membrane association domains (HDs), to diffuse between the organelles. However, how proteins partition between ER and LDs is not understood. Here, we employed synthetic model systems and found that HD-containing proteins strongly prefer monolayers and returning to the bilayer is unfavorable. This preference for monolayers is due to a higher affinity of HDs for TG over membrane phospholipids. Protein distribution is regulated by PC/PE ratio via alterations in monolayer packing and HD-TG interaction. Thus, HD-containing proteins appear to non-specifically accumulate to the LD surface. In cells, protein editing mechanisms at the ER membrane would be necessary to prevent unspecific relocation of HD-containing proteins to LDs., Triacylglycerols (TG) are synthesized at the endoplasmic reticulum (ER) bilayer and packaged into monolayer lipid droplets (LDs), but how proteins partition between ER and LDs is poorly understood. Here authors use synthetic model systems and find that proteins containing hydrophobic membrane association domains strongly prefer monolayers and that returning to the bilayer is unfavorable.

Published
2020
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15. Membrane Asymmetry Imposes Directionality on Lipid Droplet Emergence from the ER

Author

Pedro Carvalho, Sihui Wang, Rainer D. Beck, Luca Monticelli, Joana Veríssimo Ferreira, Dalila Ajjaji, Mathias Beller, Errin Johnson, Abdou Rachid Thiam, Aymeric Chorlay, Mohyeddine Omrane, Kalthoum Ben M'barek, Microfluidique, Émulsion et Biologie, Laboratoire de physique de l'ENS - ENS Paris (LPENS (UMR_8023)), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Université Paris Diderot - Paris 7 (UPD7)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Université Paris Diderot - Paris 7 (UPD7), Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Sir William Dunn School of Pathology [Oxford], University of Oxford [Oxford], Universität Heidelberg [Heidelberg], Institute for Mathematical Modeling of Biological Systems [Düsseldorf], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Heinrich-Heine-Universität Düsseldorf [Düsseldorf]

Subjects
Membrane asymmetry, Carcinoma, Hepatocellular, [SDV]Life Sciences [q-bio], Plasma protein binding, Saccharomyces cerevisiae, Biology, Endoplasmic Reticulum, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Lipid droplet, Organelle, Cytosolic lipid droplets, Directionality, Animals, Humans, Molecular Biology, Cells, Cultured, Phospholipids, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Bilayer, Cell Membrane, Liver Neoplasms, Membrane Proteins, Cell Biology, Lipid Droplets, Directional budding, Cytosol, Membrane, Biophysics, Drosophila, lipids (amino acids, peptides, and proteins), 030217 neurology & neurosurgery, Developmental Biology, Lumen (unit)
Abstract

During energy bursts, neutral lipids fabricated within the ER bilayer demix to form lipid droplets (LDs). LDs bud off mainly in the cytosol where they regulate metabolism and multiple biological processes. They indeed become accessible to most enzymes and can interact with other organelles. How such directional emergence is achieved remains elusive. Here, we found that this directionality is controlled by an asymmetry in monolayer surface coverage. Model LDs emerge on the membrane leaflet of higher coverage, which is improved by the insertion of proteins and phospholipids. In cells, continuous LD emergence on the cytosol would require a constant refill of phospholipids to the ER cytosolic leaflet. Consistent with this model, cells deficient in phospholipids present an increased number of LDs exposed to the ER lumen and compensate by remodeling ER shape. Our results reveal an active cooperation between phospholipids and proteins to extract LDs from ER.

Published
2019
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16. Membrane Curvature Catalyzes Lipid Droplet Assembly

Author

Mohyeddine Omrane, Shiqian Li, Elina Ikonen, Abdou Rachid Thiam, Xin Zhou, Alexandre Santinho, Veijo T. Salo, Aymeric Chorlay, Microfluidique, Émulsion et Biologie, Laboratoire de physique de l'ENS - ENS Paris (LPENS), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), University of Helsinki, China Agricultural University (CAU), Sorbonne Université (SU), STEMM - Stem Cells and Metabolism Research Program, Department of Anatomy, Faculty of Medicine, Research Programs Unit, Lipid Trafficking Lab, Medicum, Laboratoire de physique de l'ENS - ENS Paris (LPENS (UMR_8023)), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
0301 basic medicine, DOMAINS, [SDV]Life Sciences [q-bio], BIOGENESIS, ENDOPLASMIC-RETICULUM, Nucleation, Biology, Endoplasmic Reticulum, General Biochemistry, Genetics and Molecular Biology, Seipin, SEIPIN, 03 medical and health sciences, 0302 clinical medicine, Lipid droplet, Chlorocebus aethiops, Animals, Humans, CONTACTS, CELL, Triglycerides, ComputingMilieux_MISCELLANEOUS, LIPODYSTROPHY, Bilayer, Endoplasmic reticulum, Intracellular Membranes, Lipid Droplets, FAMILY, 030104 developmental biology, Membrane, ER, Membrane curvature, COS Cells, Biophysics, GROWTH, 1182 Biochemistry, cell and molecular biology, lipids (amino acids, peptides, and proteins), 3111 Biomedicine, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, Biogenesis, HeLa Cells
Abstract

Lipid droplet (LD) biogenesis begins in the endoplasmic reticulum (ER) bilayer, but how the ER topology impacts this process is unclear. An early step in LD formation is nucleation, wherein free neutral lipids, mainly triacylglycerols (TGs) and sterol esters (SEs), condense into a nascent LD. How this transition occurs is poorly known. Here, we found that LDs preferably assemble at ER tubules, with higher curvature than ER sheets, independently of the LD assembly protein seipin. Indeed, the critical TG concentration required for initiating LD assembly is lower at curved versus flat membrane regions. In agreement with this finding, flat ER regions bear higher amounts of free TGs than tubular ones and present less LDs. By using an in vitro approach, we discovered that the presence of free TGs in tubules is energetically unfavorable, leading to outflow of TGs to flat membrane regions or condensation into LDs. Accordingly, in vitro LD nucleation can be achieved by the sole increase of membrane curvature. In contrast to TGs, the presence of free SEs is favored at tubules and increasing SE levels is inhibitory to the curvature-induced nucleation of TG LDs. Finally, we found that seipin is enriched at ER tubules and controls the condensation process, preventing excessive tubule-induced nucleation. The absence of seipin provokes erratic LD nucleation events determined by the abundance of ER tubules. In summary, our data indicate that membrane curvature catalyzes LD assembly.

Published
2020
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17. Septin 9 has two polybasic domains critical to septin filament assembly and golgi integrity

Author

Stéphane Bressanelli, Richard Charles Garratt, Raphael Guerois, Christian Poüs, Ama Gassama-Diagne, Jinchao Yu, Bruno Goud, Abdou Rachid Thiam, Amanda Souza Camara, Didier Samuel, Mohyeddine Omrane, Nassima Benzoubir, Cyntia Taveneau, Thibault Tubiana, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Laboratoire de Physique Théorique de l'ENS [École Normale Supérieure] (LPTENS), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade de São Paulo = University of São Paulo (USP), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Théorique de l'ENS (LPTENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade de São Paulo (USP), and CCSD, Accord Elsevier

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Membrane Architecture, 02 engineering and technology, macromolecular substances, Septin, 01 natural sciences, Article, Protein filament, 03 medical and health sciences, symbols.namesake, Organelle, 0103 physical sciences, lcsh:Science, POLIMERIZAÇÃO, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Functional Aspects of Cell Biology, 010304 chemical physics, Molecular Interaction, Chemistry, fungi, virus diseases, Cell Biology, Golgi apparatus, biochemical phenomena, metabolism, and nutrition, 021001 nanoscience & nanotechnology, Protein enrichment, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, Membrane, Membrane remodeling, symbols, lcsh:Q, biological phenomena, cell phenomena, and immunity, 0210 nano-technology
Abstract

Summary Septins are GTP-binding proteins involved in several membrane remodeling mechanisms. They associate with membranes, presumably using a polybasic domain (PB1) that interacts with phosphoinositides (PIs). Membrane-bound septins assemble into microscopic structures that regulate membrane shape. How septins interact with PIs and then assemble and shape membranes is poorly understood. Here, we found that septin 9 has a second polybasic domain (PB2) conserved in the human septin family. Similar to PB1, PB2 binds specifically to PIs, and both domains are critical for septin filament formation. However, septin 9 membrane association is not dependent on these PB domains, but on putative PB-adjacent amphipathic helices. The presence of PB domains guarantees protein enrichment in PI-contained membranes, which is critical for PI-enriched organelles. In particular, we found that septin 9 PB domains control the assembly and functionality of the Golgi apparatus. Our findings offer further insight into the role of septins in organelle morphology., Graphical Abstract, Highlights • Two polybasic domains mediate septin 9 interactions with PIs • Human septins have amphipathic helices suitable for membrane binding • Septin 9 polybasic domains mediate the formation of septin higher-order structures • The mutation or depletion of septin polybasic domains induces Golgi fragmentation, Membrane Architecture; Molecular Interaction; Cell Biology; Functional Aspects of Cell Biology

Published
2019
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18. Identification of a Second Conserved Polybasic Domain in Septin 9 Involved in MicrotubuleeDependent Golgi Assembly

Author

Thibault Tubiana, Juan Peng, Stéphane Bressanelli, Cyntia Taveneau, Ama Gassama-Diagne, Bruno Goud, Christian Poüs, Mohyeddine Omrane, Didier Samuel, Jinchao Yua, and Raphaël Guérois

Subjects
Chemistry, viruses, Regulator, virus diseases, macromolecular substances, biochemical phenomena, metabolism, and nutrition, Golgi apparatus, Septin, Homology (biology), Cell biology, symbols.namesake, medicine.anatomical_structure, Secretory protein, Microtubule, Organelle, symbols, medicine, biological phenomena, cell phenomena, and immunity, Nucleus
Abstract

Septins belong to a family of GTP‐binding proteins that bind to phosphoinositides (PIs) by a polybasic domain (PB1). We reported that the deletion of PB1 in septin 9 markedly reduced, its binding to PIs and its assembly. Here, using homology modelling, we reveal the presence of another polybasic domain (PB2) conserved among the different human septins. PB1 and PB2 from two distinct molecules form an extended basic cluster in the NC interface of the filament. Importantly binding of septin 9 to PIs through PB1 and PB2 is required for recruitment of microtubules to Golgi stacks and their assembly. Knockdown of septin 9 recapitulates these effects and affects nucleus/centrosomal positioning and protein secretion. Thus septin 9 could be considered as a crucial regulator of events require for membrane trafficking and organelle morphology.

Published
2018
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