Skip to main content
SpringerLink
Log in

Lantibiotics as probes for phosphatidylethanolamine

  • Review Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

Phosphatidylethanolamine (PE) is a major component in the mammalian plasma membrane. It is present mainly in the inner leaflet of the membrane bilayer in a viable, typical mammalian cell. However, accumulating evidence indicates that a number of biological events involve PE externalization. For instance, PE is concentrated at the surface of cleavage furrow between mitotic daughter cells and is correlated with the dynamics of contractile ring. In apoptotic cells, PE is exposed to the cell surface, thus providing a molecular marker for detection. In addition, PE is a cofactor in the anticoagulant mechanism, and a distinct distribution profile of PE has been documented at the blood–endothelium interface. These recent discoveries were made possible using PE-specific probes derived from duramycin and cinnamycin, which are members of type B lantibiotics. This review provides an account on the features of these PE-specific lantibiotics in the context of molecular probes for the characterization of PE on a cellular and tissue level. According to the existing data, PE is likely a versatile chemical species that plays a role in the regulation of defined biological and physiological activities. The utilities of lantibiotic-based molecular probes will help accelerate the characterization of PE as an abundant, yet elusive membrane component.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Aoki Y, Uenaka T, Aoki J, Umeda M, Inoue K (1994) A novel peptide probe for studying the transbilayer movement of phosphatidylethanolamine. J Biochem 116:291–297

    PubMed  CAS  Google Scholar 

  • Berard M, Chantome R, Marcelli A, Boffa MC (1996) Antiphosphatidylethanolamine antibodies as the only antiphospholipid antibodies. I. Association with thrombosis and vascular cutaneous diseases. J Rheumatol 23:1369–1374

    PubMed  CAS  Google Scholar 

  • Bevers EM, Comfurius P, Zwaal RF (1996) Regulatory mechanisms in maintenance and modulation of transmembrane lipid asymmetry: pathophysiological implications. Lupus 5:480–487

    PubMed  CAS  Google Scholar 

  • Bevers EM, Comfurius P, Dekkers DW et al (1999) Lipid translocation across the plasma membrane of mammalian cells. Biochim Biophys Acta 1439:317–330

    PubMed  CAS  Google Scholar 

  • Bi EF, Lutkenhaus J (1991) FtsZ ring structure associated with division in Escherichia coli. Nature 354:161–164

    Article  PubMed  CAS  Google Scholar 

  • Blankenberg FG, Katsikis PD, Tait JF, Davis RE, Naumovski L, Ohtsuki K, Kopiwoda S, Abrams MJ, Darkes M, Robbins RC, Maecker HT, Strauss HW (1998) In vivo detection and imaging of phosphatidylserine expression during programmed cell death. Proc Natl Acad Sci USA 95:6349–6354

    Article  PubMed  CAS  Google Scholar 

  • Bleeker-Rovers CP, Boerman OC, Rennen HJ, Corstens FH, Oyen WJ (2004) Radiolabeled compounds in diagnosis of infectious and inflammatory disease. Curr Pharm Des 10:2935–2950

    Article  PubMed  CAS  Google Scholar 

  • Brötz H, Josten M, Wiedemann I, Schneider U, Götz F, Bierbaum G, Sahl HG (1998) Role of lipid-bound peptidoglycan precursors in the formation of pores by nisin, epidermin and other lantibiotics. Mol Microbiol 30:317–3127

    Article  PubMed  Google Scholar 

  • Chandran KB (1993) Flow dynamics in the human aorta. J Biomech Eng 115:611–616

    Article  PubMed  CAS  Google Scholar 

  • Choung SY, Kobayashi T, Inoue J, Takemoto K, Ishitsuka H, Inoue K (1988) Hemolytic activity of a cyclic peptide Ro09–0198 isolated from Streptoverticillium. Biochim Biophys Acta 940:171–179

    Article  PubMed  CAS  Google Scholar 

  • Devaux PF (1991) Static and dynamic lipid asymmetry in cell membranes. Biochemistry 30:1163–1173

    Article  PubMed  CAS  Google Scholar 

  • Emoto K, Umeda M (2000) An essential role for a membrane lipid in cytokinesis. Regulation of contractile ring disassembly by redistribution of phosphatidylethanolamine. J Cell Biol 149:1215–1224

    Article  PubMed  CAS  Google Scholar 

  • Emoto K, Kobayashi T, Yamaji A, Aizawa H, Yahara I, Inoue K, Umeda M (1996) Redistribution of phosphatidylethanolamine at the cleavage furrow of dividing cells during cytokinesis. Proc Natl Acad Sci USA 93:12867–12872

    Article  PubMed  CAS  Google Scholar 

  • Emoto K, Toyama-Sorimachi N, Karasuyama H, Inoue K, Umeda M (1997) Exposure of phosphatidylethanolamine on the surface of apoptotic cells. Exp Cell Res 232:430–434

    Article  PubMed  CAS  Google Scholar 

  • Emoto K, Inadome H, Kanaho Y, Narumiya S, Umeda M (2005) Local change in phospholipid composition at the cleavage furrow is essential for completion of cytokinesis. J Biol Chem 280:37901–37907

    Article  PubMed  CAS  Google Scholar 

  • Esmon NL, Smirnov MD, Esmon CT (1997a) Lupus anticoagulants and thrombosis: the role of phospholipids. Haematologica 82:474–477

    PubMed  CAS  Google Scholar 

  • Esmon NL, Smirnov MD, Esmon CT (1997b) Thrombogenic mechanisms of antiphospholipid antibodies. Thromb Haemost 78:79–82

    PubMed  CAS  Google Scholar 

  • Esmon NL, Smirnov MD, Safa O, Esmon CT (1999) Lupus anticoagulants, thrombosis and the protein C system. Haematologica 84:446–451

    PubMed  CAS  Google Scholar 

  • Hachulla E, Harle JR, Sie P, Boffa MC (2007) Antiphosphatidylethanolamine antibodies are associated with an increased odds ratio for thrombosis. A multicenter study with the participation of the European Forum on antiphospholipid antibodies. Thromb Haemost 97:949–954

    PubMed  Google Scholar 

  • Hayashi F, Nagashima K, Terui Y, Kawamura Y, Matsumoto K, Itazaki H (1990) The structure of PA48009: the revised structure of duramycin. J Antibiot 43:1421–1430

    PubMed  CAS  Google Scholar 

  • Hosoda K, Ohya M, Kohno T, Maeda T, Endo S, Wakamatsu K (1996) Structure determination of an immunopotentiator peptide, cinnamycin, complexed with lysophosphatidylethanolamine by 1H-NMR1. J Biochem 119:226–230

    PubMed  CAS  Google Scholar 

  • Iwamoto K, Kobayashi S, Fukuda R, Umeda M, Kobayashi T, Ohta A (2004) Local exposure of phosphatidylethanolamine on the yeast plasma membrane is implicated in cell polarity. Genes Cells 9:891–903

    Article  PubMed  CAS  Google Scholar 

  • Johnson LL, Schofield L, Donahay T, Narula N, Narula J (2005) 99mTc-annexin V imaging for in vivo detection of atherosclerotic lesions in porcine coronary arteries. J Nucl Med 46:1186–1193

    PubMed  Google Scholar 

  • Kaletta C, Entian KD, Jung G (1991) Prepeptide sequence of cinnamycin (Ro 09–0198): the first structural gene of a duramycin-type lantibiotic. Eur J Biochem 199:411–415

    Article  PubMed  CAS  Google Scholar 

  • Kato U, Emoto K, Fredriksson C, Nakamura H, Ohta A, Kobayashi T, Murakami-Murofushi K, Kobayashi T, Umeda M (2002) A novel membrane protein, Ros3p, is required for phospholipid translocation across the plasma membrane in Saccharomyces cerevisiae. J Biol Chem 277:37855–37862

    Article  PubMed  CAS  Google Scholar 

  • Kiestelaer BL, Reutelingsperger CPM, Heidendal GAK, Daemen MJAP, Mess WH, Hofstra L (2004) Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis. N Engl J Med 350:1472–1473

    Google Scholar 

  • Li Z, Wells CW, Esmon CT, Zhao M (2009) Phosphatidylethanolamine at the endothelial surface of aortic flow dividers. J Thromb Haemost 7:227–229

    Article  PubMed  CAS  Google Scholar 

  • Li Z, Wells CW, North PE, Kumar S, Duris CB, McIntyre JA, Zhao M (2010) Phosphatidylethanolamine at the luminal endothelial surface—implications in hemostasis and thrombotic autoimmunity. Clin Appl Thromb Hem (in press)

  • Liu S, Edwards DS (1999) 99mTc-labeled small peptides as diagnostic radiopharmaceuticals. Chem Rev 99:2235–2268

    Article  PubMed  CAS  Google Scholar 

  • Liu Z, Zhao M, Zhu X, Furenlid LR, Chen YC, Barrett HH (2007) In vivo dynamic imaging of myocardial cell death using 99mTc-labeled C2A domain of synaptotagmin I in a rat model of ischemia and reperfusion. Nucl Med Biol 34:907–915

    Article  PubMed  CAS  Google Scholar 

  • Machaidze G, Seelig J (2003) Specific binding of cinnamycin (Ro 09–0198) to phosphatidylethanolamine. Comparison between micellar and membrane environments. Biochemistry 42:12570–12576

    Article  PubMed  CAS  Google Scholar 

  • Marconescu A, Thorpe PE (2008) Coincident exposure of phosphatidylethanolamine and anionic phospholipids on the surface of irradiated cells. Biochim Biophys Acta 1778:2217–2224

    Article  PubMed  CAS  Google Scholar 

  • Maulik N, Kagan VE, Tyurin VA, Das DK (1998) Redistribution of phosphatidylethanolamine and phosphatidylserine precedes reperfusion-induced apoptosis. Am J Physiol 274:H242–H248

    PubMed  CAS  Google Scholar 

  • Mileykovskaya E, Sun Q, Margolin W, Dowhan W (1998) Localization and function of early cell division proteins in filamentous Escherichia coli cells lacking phosphatidylethanolamine. J Bacteriol 180:4252–4257

    PubMed  CAS  Google Scholar 

  • Narula J, Acio ER, Narula N, Samuels LE, Fyfe B, Wood D, Fitzpatrick JM, Raghunath PN, Tomaszewski JE, Kelly C, Steinmetz N, Green A, Tait JF, Leppo J, Blankenberg FG, Jain D, Strauss HW (2001) Annexin-V imaging for noninvasive detection of cardiac allograft rejection. Nat Med 7:1347–1352

    Article  PubMed  CAS  Google Scholar 

  • Pag U, Sahl HG (2002) Multiple activities in lantibiotics—models for the design of novel antibiotics? Curr Pharm Des 8:815–833

    Article  PubMed  CAS  Google Scholar 

  • Rouser G, Yamamoto A, Kritchevsky G (1971) Cellular membranes. Structure and regulation of lipid class composition species differences, changes with age, and variations in some pathological states. Arch Intern Med 127:1105–1121

    Article  PubMed  CAS  Google Scholar 

  • Sahl HG, Bierbaum G (1998) Lantibiotics: biosynthesis and biological activities of uniquely modified peptides from gram-positive bacteria. Annu Rev Microbiol 52:41–79

    Article  PubMed  CAS  Google Scholar 

  • Sahu SK, Gummadi SN, Manoj N, Aradhyam GK (2007) Phospholipid scramblases: an overview. Arch Biochem Biophys 462:103–114

    Article  PubMed  CAS  Google Scholar 

  • Sanmarco M, Alessi MC, Harle JR, Sapin C, Aillaud MF, Gentile S, Juhan-Vague I, Weiller PJ (2001) Antibodies to phosphatidylethanolamine as the only antiphospholipid antibodies found in patients with unexplained thromboses. Thromb Haemost 85:800–805

    PubMed  CAS  Google Scholar 

  • Seelig J (2004) Thermodynamics of lipid-peptide interactions. Biochim Biophys Acta 1666:40–50

    Article  PubMed  CAS  Google Scholar 

  • Smirnov MD, Esmon CT (1994) Phosphatidylethanolamine incorporation into vesicles selectively enhances factor Va inactivation by activated protein C. J Biol Chem 269:816–819

    PubMed  CAS  Google Scholar 

  • Smirnov MD, Triplett DT, Comp PC, Esmon NL, Esmon CT (1995) On the role of phosphatidylethanolamine in the inhibition of activated protein C activity by antiphospholipid antibodies. J Clin Invest 95:309–316

    Article  PubMed  CAS  Google Scholar 

  • Smirnov MD, Ford DA, Esmon CT, Esmon NL (1999) The effect of membrane composition on the hemostatic balance. Biochemistry 38:3591–3598

    Article  PubMed  CAS  Google Scholar 

  • Song Z, Steller H (1999) Death by design: mechanism and control of apoptosis. Trends Cell Biol 9:M49–M52

    Article  PubMed  CAS  Google Scholar 

  • Sosnovik DE, Schellenberger EA, Nahrendorf M, Novikov MS, Matsui T, Dai G, Reynolds F, Grazette L, Rosenzweig A, Weissleder R, Josephson L (2005) Magnetic resonance imaging of cardiomyocyte apoptosis with a novel magneto-optical nanoparticle. Magn Reson 54:718–724

    Article  Google Scholar 

  • Spector AA, Yorek MA (1985) Membrane lipid composition and cellular function. J Lipid Res 26:1015–1035

    PubMed  CAS  Google Scholar 

  • Sugi T, Katsunuma J, Izumi S, McIntyre JA, Makino T (1999) Prevalence and heterogeneity of antiphosphatidylethanolamine antibodies in patients with recurrent early pregnancy losses. Fertil Steril 71:1060–1065

    Article  PubMed  CAS  Google Scholar 

  • Sugi T, Matsubayashi H, Inomo A, Dan L, Makino T (2004) Antiphosphatidylethanolamine antibodies in recurrent early pregnancy loss and mid-to-late pregnancy loss. J Obstet Gynaecol Res 30:326–332

    Article  PubMed  Google Scholar 

  • Thimister PW, Hofstra L, Liem IH, Boersma HH, Kemerink G, Reutelingsperger CP, Heidendal GA (2003) In vivo detection of cell death in the area at risk in acute myocardial infarction. J Nucl Med 44:391–396

    PubMed  Google Scholar 

  • Tian Y, Jackson P, Gunter C, Wang J, Rock CO, Jackowski S (2006) Placental thrombosis and spontaneous fetal death in mice deficient in ethanolamine kinase 2. J Biol Chem 281:28438–28449

    Article  PubMed  CAS  Google Scholar 

  • Umeda M, Emoto K (1999) Membrane phospholipid dynamics during cytokinesis: regulation of actin filament assembly by redistribution of membrane surface phospholipid. Chem Phys Lipids 101:81–91

    Article  PubMed  CAS  Google Scholar 

  • Vinatier D, Dufour P, Cosson M, Houpeau JL (2001) Antiphospholipid syndrome and recurrent miscarriages. Eur J Obstet Gynecol Reprod Biol 96:37–50

    Article  PubMed  CAS  Google Scholar 

  • Wakamatsu K, Choung SY, Kobayashi T, Inoue K, Higashijima T, Miyazawa T (1990) Complex formation of peptide antibiotic Ro09–0198 with lysophosphatidylethanolamine: 1H NMR analyses in dimethyl sulfoxide solution. Biochemistry 29:113–118

    Article  PubMed  CAS  Google Scholar 

  • Widdick DA, Dodd HM, Barraille P, White J, Stein TH, Chater KF, Gasson MJ, Bibb MJ (2003) Cloning and engineering of the cinnamycin biosynthetic gene cluster from Streptomyces cinnamoneus cinnamoneus DSM 40005. Proc Natl Acad Sci USA 100:4316–4321

    Article  PubMed  CAS  Google Scholar 

  • Williamson P, Schlegel RA (2002) Transbilayer phospholipid movement and the clearance of apoptotic cells. Biochim Biophys 1585:53–63

    CAS  Google Scholar 

  • Wyllie AH (1997) Apoptosis: an overview. Br Med Bull 53:451–465

    PubMed  CAS  Google Scholar 

  • Zhao M, Beauregard DA, Loizou L, Davletov B, Brindle KM (2001) Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent. Nat Med 7:1241–1244

    Article  PubMed  CAS  Google Scholar 

  • Zhao M, Zhu X, Ji S, Zhou J, Ozker KS, Fang W, Molthen RC, Hellman RS (2006) 99mTc-labeled C2A domain of synaptotagmin I as a target-specific molecular probe for noninvasive imaging of acute myocardial infarction. J Nucl Med 47:1367–1374

    PubMed  CAS  Google Scholar 

  • Zhao M, Li Z, Bugenhagen S (2008) 99mTc-labeled duramycin as a novel phosphatidylethanolamine-binding molecular probe. J Nucl Med 49:1345–1352

    Article  PubMed  CAS  Google Scholar 

  • Zimmermann N, Freund S, Fredenhagen A, Jung G (1993) Solution structures of the lantibiotics duramycin B and C. Eur J Biochem 216:419–428

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

Funding support from the National Institutes of Health is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    Ming Zhao

Authors
  1. Ming Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ming Zhao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, M. Lantibiotics as probes for phosphatidylethanolamine. Amino Acids 41, 1071–1079 (2011). https://doi.org/10.1007/s00726-009-0386-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-009-0386-9

Keywords

Search

Navigation