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Ceramide in Plasma Membrane Repair

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Sphingolipids in Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 216))

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Abstract

The perforation of the plasmalemma by pore-forming toxins causes an influx of Ca2+ and an efflux of cytoplasmic proteins. In order to ensure cellular survival, lesions have to be identified, plugged and removed from the membrane. The Ca2+-driven fusion of lysosomes with the plasma membrane leads to hydrolysis of sphingomyelin by acid sphingomyelinase and a formation of ceramide platforms in the outer leaflet of the lipid bilayer. We propose that the negative curvature, promoted by tighter packing of lipids in the outer layer, leads to an inward vesiculation of the damaged area for its endocytotic uptake and internal degradation. In contrast, the activation of neutral sphingomyelinase triggers the production of ceramide within the inner leaflet of the lipid bilayer, thereby promoting an outward curvature, which enables the cell to shed the membrane-containing toxin pore into the extracellular space. In this process, ceramide is supported by members of the annexin protein family which act as Ca2+ sensors and as membrane fusion agents.

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References

  • Abdel Shakor AB, Kwiatkowska K, Sobota A (2004) Cell surface ceramide generation precedes and controls FcgammaRII clustering and phosphorylation in rafts. J Biol Chem 279:36778–36787

    Article  PubMed  CAS  Google Scholar 

  • Andrieu-Abadie N, Levade T (2002) Sphingomyelin hydrolysis during apoptosis. Biochim Biophys Acta 1585:126–134

    Article  PubMed  CAS  Google Scholar 

  • Ashida H, Mimuro H, Ogawa M, Kobayashi T, Sanada T, Kim M, Sasakawa C (2011) Host-pathogen interactions: cell death and infection: a double-edged sword for host and pathogen survival. J Cell Biol. doi:10.1083/jcb.201108081:

  • Babiychuk EB, Monastyrskaya K, Draeger A (2008) Fluorescent annexin A1 reveals dynamics of ceramide platforms in living cells. Traffic 9:1757–1775

    Article  PubMed  CAS  Google Scholar 

  • Babiychuk EB, Monastyrskaya K, Potez S, Draeger A (2009) Intracellular Ca(2+) operates a switch between repair and lysis of streptolysin O-perforated cells. Cell Death Differ 16:1126–1134

    Article  PubMed  CAS  Google Scholar 

  • Babiychuk EB, Monastyrskaya K, Potez S, Draeger A (2010) Blebbing confers resistance against cell lysis. Cell Death Differ 18:80–89

    Article  PubMed  Google Scholar 

  • Babiychuk EB, Atanassoff AP, Monastyrskaya K, Brandenberger C, Studer D, Allemann C, Draeger A (2011) The targeting of plasmalemmal ceramide to mitochondria during apoptosis. PLoS One 6:e23706

    Article  PubMed  CAS  Google Scholar 

  • Bezombes C, Grazide S, Garret C, Fabre C, Quillet-Mary A, Muller S, Jaffrezou JP, Laurent G (2004) Rituximab antiproliferative effect in B-lymphoma cells is associated with acid-sphingomyelinase activation in raft microdomains. Blood 104:1166–1173

    Article  PubMed  CAS  Google Scholar 

  • Bleicken S, Classen M, Padmavathi PV, Ishikawa T, Zeth K, Steinhoff HJ, Bordignon E (2010) Molecular details of Bax activation, oligomerization, and membrane insertion. J Biol Chem 285:6636–6647

    Article  PubMed  CAS  Google Scholar 

  • Borgonovo B, Cocucci E, Racchetti G, Podini P, Bachi A, Meldolesi J (2002) Regulated exocytosis: a novel, widely expressed system. Nat Cell Biol 4:955–962

    Article  PubMed  CAS  Google Scholar 

  • Caler EV, Chakrabarti S, Fowler KT, Rao S, Andrews NW (2001) The Exocytosis-regulatory protein synaptotagmin VII mediates cell invasion by Trypanosoma cruzi. J Exp Med 193:1097–1104

    Article  PubMed  CAS  Google Scholar 

  • Chamberlain LH, Burgoyne RD, Gould GW (2001) SNARE proteins are highly enriched in lipid rafts in PC12 cells: implications for the spatial control of exocytosis. Proc Natl Acad Sci USA 98:5619–5624

    Article  PubMed  CAS  Google Scholar 

  • Chambers R (1917) Microdissection studies. I. The visible structure of cell protoplasm and death changes. Am J Physiol 43:1–12

    CAS  Google Scholar 

  • Chernomordik LV, Kozlov MM (2008) Mechanics of membrane fusion. Nat Struct Mol Biol 15:675–683

    Article  PubMed  CAS  Google Scholar 

  • Draeger A, Monastyrskaya K, Babiychuk EB (2011) Plasma membrane repair and cellular damage control: the annexin survival kit. Biochem Pharmacol 81:703–712

    Article  PubMed  CAS  Google Scholar 

  • Fernandes MC, Cortez M, Flannery AR, Tam C, Mortara RA, Andrews NW (2011) Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion. J Exp Med 208:909–921

    Article  PubMed  CAS  Google Scholar 

  • Fine M, Llaguno MC, Lariccia V, Lin MJ, Yaradanakul A, Hilgemann DW (2011) Massive endocytosis driven by lipidic forces originating in the outer plasmalemmal monolayer: a new approach to membrane recycling and lipid domains. J Gen Physiol 137:137–154

    Article  PubMed  CAS  Google Scholar 

  • Freche B, Reig N, van der Goot FG (2007) The role of the inflammasome in cellular responses to toxins and bacterial effectors. Semin Immunopathol 29:249–260

    Article  PubMed  CAS  Google Scholar 

  • Gil C, Cubi R, Blasi J, Aguilera J (2006) Synaptic proteins associate with a sub-set of lipid rafts when isolated from nerve endings at physiological temperature. Biochem Biophys Res Commun 348:1334–1342

    Article  PubMed  CAS  Google Scholar 

  • Goni FM, Alonso A (2009) Effects of ceramide and other simple sphingolipids on membrane lateral structure. Biochim Biophys Acta 1788:169–177

    Article  PubMed  CAS  Google Scholar 

  • Grassme H, Jekle A, Riehle A, Schwarz H, Berger J, Sandhoff K, Kolesnick R, Gulbins E (2001) CD95 signaling via ceramide-rich membrane rafts. J Biol Chem 276:20589–20596

    Article  PubMed  CAS  Google Scholar 

  • Grassme H, Jendrossek V, Bock J, Riehle A, Gulbins E (2002) Ceramide-rich membrane rafts mediate CD40 clustering. J Immunol 168:298–307

    PubMed  CAS  Google Scholar 

  • Grassme H, Riethmuller J, Gulbins E (2007) Biological aspects of ceramide-enriched membrane domains. Prog Lipid Res 46:161–170

    Article  PubMed  CAS  Google Scholar 

  • Gulbins E, Kolesnick R (2003) Raft ceramide in molecular medicine. Oncogene 22:7070–7077

    Article  PubMed  CAS  Google Scholar 

  • Gulbins E, Li PL (2006) Physiological and pathophysiological aspects of ceramide. Am J Physiol Regul Integr Comp Physiol 290:R11–R26

    Article  PubMed  CAS  Google Scholar 

  • Hannun YA, Obeid LM (2008) Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 9:139–150

    Article  PubMed  CAS  Google Scholar 

  • Hilgemann DW, Fine M (2011) Mechanistic analysis of massive endocytosis in relation to functionally defined surface membrane domains. J Gen Physiol 137:155–172

    Article  PubMed  CAS  Google Scholar 

  • Holopainen JM, Angelova MI, Kinnunen PK (2000) Vectorial budding of vesicles by asymmetrical enzymatic formation of ceramide in giant liposomes. Biophys J 78:830–838

    Article  PubMed  CAS  Google Scholar 

  • Idone V, Tam C, Goss JW, Toomre D, Pypaert M, Andrews NW (2008) Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis. J Cell Biol 180:905–914

    Article  PubMed  CAS  Google Scholar 

  • Janmey PA, Kinnunen PK (2006) Biophysical properties of lipids and dynamic membranes. Trends Cell Biol 16:538–546

    Article  PubMed  CAS  Google Scholar 

  • Keyel PA, Heid ME, Salter RD (2011) Macrophage responses to bacterial toxins: a balance between activation and suppression. Immunol Res 50:118–123

    Article  PubMed  CAS  Google Scholar 

  • Kirschnek S, Paris F, Weller M, Grassme H, Ferlinz K, Riehle A, Fuks Z, Kolesnick R, Gulbins E (2000) CD95-mediated apoptosis in vivo involves acid sphingomyelinase. J Biol Chem 275:27316–27323

    PubMed  CAS  Google Scholar 

  • Kolesnick RN, Goni FM, Alonso A (2000) Compartmentalization of ceramide signaling: physical foundations and biological effects. J Cell Physiol 184:285–300

    Article  PubMed  CAS  Google Scholar 

  • Lariccia V, Fine M, Magi S, Lin MJ, Yaradanakul A, Llaguno MC, Hilgemann DW (2011) Massive calcium-activated endocytosis without involvement of classical endocytic proteins. J Gen Physiol 137:111–132

    Article  PubMed  CAS  Google Scholar 

  • Lewis RS (2003) Calcium oscillations in T-cells: mechanisms and consequences for gene expression. Biochem Soc Trans 31:925–929

    Article  PubMed  CAS  Google Scholar 

  • Li R, Blanchette-Mackie EJ, Ladisch S (1999) Induction of endocytic vesicles by exogenous C(6)-ceramide. J Biol Chem 274:21121–21127

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Montero I, Rodriguez N, Cribier S, Pohl A, Velez M, Devaux PF (2005) Rapid transbilayer movement of ceramides in phospholipid vesicles and in human erythrocytes. J Biol Chem 280:25811–25819

    Article  PubMed  CAS  Google Scholar 

  • Lorusso A, Covino C, Priori G, Bachi A, Meldolesi J, Chieregatti E (2006) Annexin2 coating the surface of enlargeosomes is needed for their regulated exocytosis. EMBO J 25:5443–5456

    Article  PubMed  CAS  Google Scholar 

  • McNeil PL, Kirchhausen T (2005) An emergency response team for membrane repair. Nat Rev Mol Cell Biol 6:499–505

    Article  PubMed  CAS  Google Scholar 

  • McNeil PL, Steinhardt RA (2003) Plasma membrane disruption: repair, prevention, adaptation. Annu Rev Cell Dev Biol 19:697–731

    Article  PubMed  CAS  Google Scholar 

  • McNeil AK, Rescher U, Gerke V, McNeil PL (2006) Requirement for annexin A1 in plasma membrane repair. J Biol Chem 281:35202–35207

    Article  PubMed  CAS  Google Scholar 

  • Morgan BP (1989) Complement membrane attack on nucleated cells: resistance, recovery and non-lethal effects. Biochem J 264:1–14

    PubMed  CAS  Google Scholar 

  • Morgan BP, Luzio JP, Campbell AK (1986) Intracellular Ca2+ and cell injury: a paradoxical role of Ca2+ in complement membrane attack. Cell Calcium 7:399–411

    Article  PubMed  CAS  Google Scholar 

  • Morgan BP, Dankert JR, Esser AF (1987) Recovery of human neutrophils from complement attack: removal of the membrane attack complex by endocytosis and exocytosis. J Immunol 138:246–253

    PubMed  CAS  Google Scholar 

  • Ninomiya Y, Kishimoto T, Miyashita Y, Kasai H (1996) Ca2+-dependent exocytotic pathways in Chinese hamster ovary fibroblasts revealed by a caged-Ca2+ compound. J Biol Chem 271:17751–17754

    Article  PubMed  CAS  Google Scholar 

  • Paris F, Grassme H, Cremesti A, Zager J, Fong Y, Haimovitz-Friedman A, Fuks Z, Gulbins E, Kolesnick R (2001) Natural ceramide reverses Fas resistance of acid sphingomyelinase(−/−) hepatocytes. J Biol Chem 276:8297–8305

    Article  PubMed  CAS  Google Scholar 

  • Pedrosa Ribeiro CMP, McKay RR, Hosoki E, Bird GS, Putney JW (2000) Effects of elevated cytoplasmic calcium and protein kinase C on endoplasmic reticulum structure and function in HEK293 cells. Cell Calcium 27:175–185

    Article  Google Scholar 

  • Perrotta C, Bizzozero L, Cazzato D, Morlacchi S, Assi E, Simbari F, Zhang Y, Gulbins E, Bassi MT, Rosa P, Clementi E (2010) Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function. J Biol Chem 285:40240–40251

    Article  PubMed  CAS  Google Scholar 

  • Pilzer D, Gasser O, Moskovich O, Schifferli JA, Fishelson Z (2005) Emission of membrane vesicles: roles in complement resistance, immunity and cancer. Springer Semin Immunopathol 27:375–387

    Article  PubMed  CAS  Google Scholar 

  • Potez S, Luginbuhl M, Monastyrskaya K, Hostettler A, Draeger A, Babiychuk EB (2011) Tailored protection against plasmalemmal injury by annexins with different Ca2+ sensitivities. J Biol Chem 286:17982–17991

    Article  PubMed  CAS  Google Scholar 

  • Salaun C, Gould GW, Chamberlain LH (2005) Lipid raft association of SNARE proteins regulates exocytosis in PC12 cells. J Biol Chem 280:19449–19453

    Article  PubMed  Google Scholar 

  • Siskind LJ, Kolesnick RN, Colombini M (2002) Ceramide channels increase the permeability of the mitochondrial outer membrane to small proteins. J Biol Chem 277:26796–26803

    Article  PubMed  CAS  Google Scholar 

  • Szabadkai G, Rizzuto R (2004) Participation of endoplasmic reticulum and mitochondrial calcium handling in apoptosis: more than just neighborhood? FEBS Lett 567:111–115

    Article  PubMed  CAS  Google Scholar 

  • Tam C, Idone V, Devlin C, Fernandes MC, Flannery A, He X, Schuchman E, Tabas I, Andrews NW (2010) Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair. J Cell Biol 189:1027–1038

    Article  PubMed  CAS  Google Scholar 

  • Tang N, Ong WY, Zhang EM, Chen P, Yeo JF (2007) Differential effects of ceramide species on exocytosis in rat PC12 cells. Exp Brain Res 183:241–247

    Article  PubMed  CAS  Google Scholar 

  • Tepper AD, Ruurs P, Wiedmer T, Sims PJ, Borst J, van Blitterswijk WJ (2000) Sphingomyelin hydrolysis to ceramide during the execution phase of apoptosis results from phospholipid scrambling and alters cell-surface morphology. J Cell Biol 150:155–164

    Article  PubMed  CAS  Google Scholar 

  • Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brugger B, Simons M (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–1247

    Article  PubMed  CAS  Google Scholar 

  • van Blitterswijk WJ, van der Luit AH, Veldman RJ, Verheij M, Borst J (2003) Ceramide: second messenger or modulator of membrane structure and dynamics? Biochem J 369:199–211

    Article  PubMed  Google Scholar 

  • Walev I, Tappe D, Gulbins E, Bhakdi S (2000) Streptolysin O-permeabilized granulocytes shed L-selectin concomitantly with ceramide generation via neutral sphingomyelinase. J Leukoc Biol 68:865–872

    PubMed  CAS  Google Scholar 

  • Walev I, Bhakdi SC, Hofmann F, Djonder N, Valeva A, Aktories K, Bhakdi S (2001) Delivery of proteins into living cells by reversible membrane permeabilization with streptolysin-O. Proc Natl Acad Sci USA 98:3185–3190

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cell Biology, Institute of Anatomy, University of Bern, Baltzerstr. 2, 3012, Bern, Switzerland

    Annette Draeger & Eduard B. Babiychuk

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  1. Annette Draeger
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  2. Eduard B. Babiychuk
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Correspondence to Annette Draeger .

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Editors and Affiliations

  1. , Department of Molecular Biology, University of Duisburg-Essen, Hufelandstraße 55, Essen, 45122, Germany

    Erich Gulbins

  2. Division of Pulmonary, Allergy, Critical, Department of Medicine, Indiana University School of Medicine, W. Walnut Street 980, Indianapolis, 46202, Indiana, USA

    Irina Petrache

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Draeger, A., Babiychuk, E.B. (2013). Ceramide in Plasma Membrane Repair. In: Gulbins, E., Petrache, I. (eds) Sphingolipids in Disease. Handbook of Experimental Pharmacology, vol 216. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1511-4_17

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