Ganglioside GM1 increases line tension at raft boundary in model membranes

被引:10
作者
Akimov S.A. [1 ]
Hlaponin E.A. [1 ]
Bashkirov P.V. [1 ]
Boldyrev I.A. [2 ]
Mikhalyov I.I. [2 ]
Telford W.G. [3 ]
Molotkovskaya I.M. [2 ]
机构
[1] Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Moscow 119991
[2] Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997
[3] Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
基金
美国国家卫生研究院; 俄罗斯基础研究基金会;
关键词
Apoptosis; Ganglioside; Line tension; Raft;
D O I
10.1134/S1990747809020159
中图分类号
学科分类号
摘要
Gangliosides are significant participants in suppression of immune system during tumor processes. It was shown that they can induce apoptosis of T-lymphocytes in a raft-dependent manner. Fluorescence confocal microscopy was used to study distribution and influence of ganglioside GM1 on raft properties in giant unilamellar vesicles. Both raft and non-raft phase markers were utilized. No visible phase separation was observed without GM1 unless lateral tension was applied to the membrane. At 2 mol % of GM1 large domains appeared indicating macroscopic phase separation. Increase of GM1 content to 5 mol % resulted in shape transformation of the domains consistent with growth of line tension at the domain boundary. At 10 mol % of GM1 almost all domains were pinched out from vesicles, forming their own homogeneous liposomes. Estimations showed that the change of the GM1 content from 2 to 5-10 mol % resulted in a several-fold increase of line tension. This finding provides a possible mechanism of apoptosis induction by GM1. Incorporation of GM1 into a membrane leads to an increase of the line tension. This results in a growth of the average size of rafts due to coalescence or merger of small domains. Thus, necessary proteins can find themselves in one common raft and start the corresponding cascade of reactions. © Pleiades Publishing, Ltd. 2009.
引用
收藏
页码:216 / 222
页数:6
相关论文
共 31 条
  • [1] Igney F.H., Krammer P.H., Death and Anti-Death: Tumor Resistance to Apoptosis, Nat. Rev. Cancer, 2, pp. 277-288, (2002)
  • [2] Birkle S., Zeng G., Gao L., Yu R.K., Aubry J., Role of Tumor-Associated Gangliosides in Cancer Progression, Biochimie, 85, pp. 455-463, (2003)
  • [3] Ladisch S., Kitada S., Hays E.F., Gangliosides Shed by Tumor Cells Enhance Tumour Formation in Mice, J. Clin. Invest., 79, pp. 1879-1882, (1987)
  • [4] Heitger A., Ladisch S., Gangliosides Block Antigen Presentation by Human Monocytes, Biochim. Biophys. Acta, 1303, pp. 161-168, (1996)
  • [5] Hueber A.O., Bernard A.M., Herincs Z., Couzinet A., He H.T., An Essential Role for Membrane Rafts in the Initiation of Fas/ CD95-Triggered Cell Death in Mouse Thymocytes, EMBO Rep., 3, pp. 190-196, (2002)
  • [6] Grassme H., Jekle A., Riehle A., Schwarz H., Berger J., Sandho K., Kolesnick R., Gulbins E., CD95 Signaling via Ceramide Rich Membrane Rafts, J. Biol. Chem., 276, pp. 20589-20596, (2001)
  • [7] Burek C., Roth J., Koch H.G., Harzer K., Los M., Shlutze-Osthoff K., The Role of Ceramide in Receptor- and Stress-Induced Apoptosis Studied in Acidic Ceramidase Farber Desease Cells, Oncogene, 20, pp. 6493-6502, (2001)
  • [8] Hartel S., Fanani M.L., Maggio B., Shape Transitions and Lattice Structuring of Ceramide-Enriched Domains Generated by Sphingomielinase in Lipid Monolayers, Biophys. J., 88, pp. 287-304, (2005)
  • [9] London E., Insights into Lipid Raft Structure and Formation from Experiments in Model Membranes, Curr. Opin. Struct. Biol., 12, pp. 480-486, (2002)
  • [10] Brown D.A., London E., Structure and Origin of Ordered Lipid Domains in Biological Membranes, J. Membr. Biol., 164, pp. 103-114, (1998)