Lipid raft

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Model of the lipid rafts . Legend: (A) cytoplasm, (B) extracellular space, (1) normal cell membrane, (2) lipid raft, (3) lipid raft membrane protein, (4) membrane protein, (5) carbohydrate modification of glycoprotein (glycosylation), (6 ) Glycoprotein linked by GPI anchor, (7) cholesterol, (8) carbohydrate modification of a glycolipid.

Lipid rafts are called special areas in cell membranes . They are characterized by a relatively high content of sphingomyelins , glycosphingolipids and cholesterol .

properties

Lipid rafts arrange themselves as a liquid crystalline phase in their own areas of the cell membrane. You are involved in various processes, e.g. B. Sorting of proteins for the cell membrane in the Golgi apparatus , endocytosis and signal transduction . They are currently defined as dynamically ordered nanostructures made up of sterols and sphingolipids with specific membrane proteins that can fuse through lipid -lipid , protein-lipid, and protein-protein interactions . Due to their relative stability to extraction with surfactants , lipid rafts were also referred to as detergent-insoluble membranes, detergent-resistant membranes, glycosphingolipids-enriched membranes, detergent-insoluble glycolipid-rich membranes , and Triton-insoluble floating fraction . Proteins with GPI anchors tend to accumulate in lipid rafts .

Although the exact model is unknown, minimize lipid rafts , the free energy between the two phases - are formed domains of a typical size, neither mix even further merge itself. The lipid rafts form an ordered phase within the disordered phase of the phospholipids of the remaining cell membrane. The segregation between the " liquid ordered phase " (ordered phase, L0) and the " liquid disordered phase " "(disordered phase, Ld or Lα) can be clearly observed. Due to their comparatively greater thickness, the lipid rafts possibly offer a sorting mechanism for membrane proteins the length of their transmembrane domain .

analysis

Problems with the representation of lipid rafts are the lack of thermodynamic equilibrium in the composition of the cell membrane, which makes the investigation of the composition difficult. In addition, artificial membranes have a lower number of membrane proteins than natural ones.

Their small size of 10–200 nm makes it difficult to observe them because they are close to the resolution of classic light microscopes . However, fluorescence microscopy offers a possibility to make lipid rafts visible. Are used z. B. Dyes that are embedded between the domains such as Laurdan , Filipin or head-labeled dyes such as Texas Red , which, due to their size, are preferentially embedded in the disordered phase. The B-subunit of the cholera toxin binds to the ganglioside GM1 in lipid rafts . A fluorescent label can be used to mark proteins that accumulate in lipid rafts , e.g. B. Lck-GFP . Cholesterol can be bound by Filipin, Nystatin or Amphotericin B. Methyl-beta- cyclodextrin can remove cholesterol from the cell membrane. The biosynthesis of cholesterol can be inhibited by HMG-CoA reductase inhibitors . In contrast to the other areas of the cell membrane, lipid rafts are insoluble in a 1% (m / V) Triton X-100 solution at 4 ° C and can therefore be isolated with mild surfactants .

Methods frequently used for analysis are e.g. B. fluorescence microscopy , fluorescence correlation spectroscopy and cross correlation spectroscopy (FCS / FCCS) to measure mobility, Förster resonance energy transfer to measure the proximity of two molecules and optical tweezers to measure viscosity . Furthermore, is atomic force microscopy , the scanning ion conductance microscopy (SICM) and the dual polarization interferometry , nuclear magnetic resonance spectroscopy as well as ELISA , Western blot and FACS used. Per FLIP or FRAP lateral mobility can be tracked.

Criticism of the Lipid Raft concept

Various points were criticized about the concept of lipid rafts . Although lipid rafts can be observed in model membranes under a fluorescence microscope, their detection in living cells has not yet been clearly demonstrated. Researchers have not yet agreed on their average size (1–1000 nm) and lifespan. It is therefore unclear in what form lipid rafts exist.

history

Special areas of a cell membrane ( english membrane micro domain ) were first postulated in the 1970s through bull and Sackmann and Klausner and Karnovsky. Karnovsky's research group was able to show the uneven structure of the cell membrane based on the different fluorescence lifetimes of 1,6-diphenyl-1,3,5-hexatriene in the cell membrane. In 1988 Kai Simons in Germany and Gerrit van Meer in the Netherlands presented a concept of microdomains in lipid membranes in which cholesterol , glycolipids and sphingolipids accumulate. They called these domains “lipid rafts” because they float like rafts on the two-dimensional lipid bilayer of the cell membrane in the fluid mosaic model .

Individual evidence

  1. ^ S. Thomas, RS Kumar, TD Brumeanu: Role of lipid rafts in T cells. In: AITE. 52, 2004, pp. 215-224.
  2. ↑ D. Lingwood, K. Simons: Lipid rafts as a membrane-organizing principle. In: Science. Volume 327, Number 5961, January 2010, pp. 46-50, ISSN  1095-9203 . doi: 10.1126 / science.1174621 . PMID 20044567 .
  3. ↑ Linda J Pike: The Challenge of Lipid Rafts. In: Journal of Lipid Research. Oct 2008, pp. 1-17.
  4. ↑ A. Rietveld, K. Simons: The differential miscibility of lipids as the basis for the formation of functional membrane rafts. In: Biochim. Biophys. Acta . 1376 (3), November 1998, pp. 467-479. PMID 9805010 .
  5. ↑ K. Simons, JL Sampaio: Membrane organization and lipid rafts. In: Cold Spring Harbor perspectives in biology. Volume 3, Number 10, October 2011, p. A004697, ISSN  1943-0264 . doi: 10.1101 / cshperspect.a004697 . PMID 21628426 . PMC 3179338 (free full text).
  6. ↑ a b c J. A. Allen, RA Halverson-Tamboli, MM Rasenick: Lipid raft microdomains and neurotransmitter signaling. In: Nature reviews. Neuroscience. Volume 8, Number 2, February 2007, pp. 128-140, ISSN  1471-003X . doi: 10.1038 / nrn2059 . PMID 17195035 .
  7. ↑ Ken Jacobson, Ole G. Mouritsen, Richard GWAnderson: Lipid rafts: At a crossroad between cell biology and physics . In: Nature Cell Biology . tape 9 , no. 1 , 2007, p. 7-14 , doi : 10.1038 / ncb0107-7 , PMID 17199125 .
  8. ↑ a b L. J. Pike: The challenge of lipid rafts . In: The Journal of Lipid Research . tape 50 , 2008, p. S323 , doi : 10.1194 / jlr.R800040-JLR200 , PMID 18955730 , PMC 2674732 (free full text).
  9. ↑ LA Bagatolli: To see or not to see: lateral organization of biological membranes and fluorescence microscopy . In: Biochim. Biophys. Acta . tape 1758 , no. 10 , 2006, p. 1451-1456 , doi : 10.1016 / j.bbamem.2006.05.019 .
  10. ↑ G. Gimpl, K. Gehrig-Burger: Cholesterol reporter molecules. In: Bioscience Reports . Volume 27, Number 6, December 2007, pp. 335-358, ISSN  0144-8463 . doi: 10.1007 / s10540-007-9060-1 . PMID 17668316 .
  11. ↑ PA Orlandi, PH Fishman: Filipin-dependent inhibition of cholera toxin: evidence for toxin internalization and activation through caveolae-like domains. In: Journal of Cell Biology . Volume 141, Number 4, May 1998, pp. 905-915, ISSN  0021-9525 . PMID 9585410 . PMC 2132770 (free full text).
  12. ^ J. Sanchez, J. Holmgren: Cholera toxin - a foe & a friend. In: The Indian journal of medical research. Volume 133, February 2011, pp. 153-163, ISSN  0971-5916 . PMID 21415489 . PMC 3089046 (free full text).
  13. ↑ KB Kim, JS Lee, YG Ko: The isolation of detergent-resistant lipid rafts for two-dimensional electrophoresis. In: Methods in molecular biology (Clifton, NJ). Volume 424, 2008, pp. 413-422, ISSN  1064-3745 . doi : 10.1007 / 978-1-60327-064-9_32 . PMID 18369879 .
  14. ↑ E. Klotzsch, GJ Schütz: A critical survey of methods to detect plasma membrane rafts. In: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. Volume 368, Number 1611, February 2013, pp. 20120033, ISSN  1471-2970 . doi: 10.1098 / rstb.2012.0033 . PMID 23267184 . PMC 3538433 (free full text).
  15. ^ S. Thomas, RS Kumar, S. Casares, T.-D. Brumeanu: Sensitive detection of GM1 lipid rafts and TCR partitioning in the T cell membrane . In: Journal of Immunological Methods . tape 275 , no. 1–2 , 2003, pp. 161-168 , doi : 10.1016 / S0022-1759 (03) 00014-0 , PMID 12667680 .
  16. ^ Sunil Thomas, Rajeev Kumar, Anca Preda-Pais, Sofia Casares, Teodor-D. Brumeanu: A Model for Antigen-Specific T-Cell Anergy: Displacement of CD4-p56 lck Signalosome from the Lipid Rafts by a Soluble, Dimeric Peptide-MHC Class II Chimera1 . In: The Journal of Immunology . tape 170 , no. 12 , 2003, p. 5981-5992 , PMID 12794125 .
  17. ↑ Sean Munro: Lipid rafts: elusive or illusive? In: Cell . tape 115 , no. 4 , 2003, p. 377-388 , doi : 10.1016 / S0092-8674 (03) 00882-1 , PMID 14622593 .
  18. ↑ A. Stier, E. Sackmann: Spin labels as enzyme substrates Heterogeneous lipid distribution in liver microsomal membranes . In: Biochimica et Biophysica Acta (BBA) - Biomembranes . tape 311 , no. 3 , 1973, p. 400-408 , doi : 10.1016 / 0005-2736 (73) 90320-9 , PMID 4354130 .
  19. ^ Morris J. Karnovsky, Alan M. Kleinfeld, Richard L. Hoover, Richard D. Klausner: The concept of lipid domains in membranes . In: The Journal of Cell Biology . tape 94 , no. 1 , 1982, pp. 1-6 , doi : 10.1083 / jcb.94.1.1 , PMID 6889603 , PMC 2112185 (free full text).
  20. ^ S. Thomas, AP Pais, S. Casares, TD Brumeanu: Analysis of lipid rafts in T cells. In: Molecular Immunology. 41, 2004, pp. 399-409.
  21. ^ Zeljka Korade: Lipid rafts, cholesterol, and the brain. In: Neuropharmacology . 55, 2008, pp. 1265-1273.

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