Lipid Rafts As a Membrane-Organizing Principle

  title={Lipid Rafts As a Membrane-Organizing Principle},
  author={Daniel Lingwood and Kai Simons},
  pages={46 - 50}
Lipid Rafts Come of Age Living cells are surrounded by cellular membranes composed of lipids and proteins. Much attention has been paid to the biogenesis and sorting of membrane proteins. The dynamics and sorting of lipids have been much more difficult to study. Lingwood and Simons (p. 46) review the evidence for, and the role played by, so-called lipid rafts—laterally segregated regions within membranes enriched for particular lipids and proteins. Cell membranes display a tremendous complexity… 

Membrane organization and lipid rafts.

The emerging principles of membrane architecture are reviewed with special emphasis on lipid organization and domain formation, which combines the potential for sphingolipid-cholesterol self-assembly with protein specificity to focus and regulate membrane bioactivity.

Mesoscale organization of domains in the plasma membrane – beyond the lipid raft

  • S. LuG. Fairn
  • Biology
    Critical reviews in biochemistry and molecular biology
  • 2018
The classical lipid raft hypothesis is discussed and alternative models of lipid-protein interactions, annular lipid shells, and larger membrane clusters are discussed including visible structures such as clathrin-coated pits and caveolae.

Continuously variable lipid packing as the principle of functional membrane heterogeneity

This work proposes continuously variable lipid packing as the principle of the functional membrane lateral heterogeneity and shows that this spectrum of membrane packing modulates the orientation of membrane lipid receptors, which ultimately influences their specific bioactivity.

The mystery of membrane organization: composition, regulation and physiological relevance of lipid rafts

The membrane raft hypothesis formalized a physicochemical principle for a subtype of lateral membrane heterogeneity, wherein the preferential associations of cholesterol and saturated lipids drives the formation of relatively packed (ordered) membrane domains that selectively recruit certain lipids and proteins.

Protein Association with Membrane Rafts

Assessment of detergent-resistant membranes (DRM), the original biochemical method to analyse raft association of a protein, is artefact-prone and therefore not suitable to prove raft involvement in a biological process.

Flotillins functionally organize the bacterial membrane

Flotillins form large, dynamic assemblies that are able to influence membrane fluidity and prevent condensation of Laurdan stained membrane regions and are identified to be responsible for lateral segregation of defined membrane domains in the model organism Bacillus subtilis.

The Origin of Lipid Rafts.

The picture that has emerged from nearest-neighbor recognition (NNR) studies is that lipid mixing is governed by a balance of these "push and pull" forces, which maximizes the number of hydrocarbon contacts and attractive van der Waals interactions within the membrane.

Greasing their way: lipid modifications determine protein association with membrane rafts.

Evidence suggesting that post-translation modification by saturated lipids recruits both peripheral and transmembrane proteins to rafts, while short, unsaturated, and/or branched hydrocarbon chains prevent raft association is reviewed.

Rafting through traffic: Membrane domains in cellular logistics.

Plasma membrane organization and function: moving past lipid rafts

  • M. Kraft
  • Biology
    Molecular biology of the cell
  • 2013
The results that challenge the lipid raft hypothesis are summarized and alternative hypothetical models of plasma membrane organization and lipid-mediated cellular function are discussed.



Order of lipid phases in model and plasma membranes

Lipid-mediated coalescence of the GM1 raft domain seems to be distinct from the formation of a Lo phase, suggesting additional interactions between proteins and lipids to be effective in raft organization.

Sphingolipid–Cholesterol Rafts Diffuse as Small Entities in the Plasma Membrane of Mammalian Cells

It is demonstrated that using protein constructs with identical ectodomains and different membrane regions and vice versa provides the viscous damping of the membrane domain in the lipid bilayer to probe the dynamics and size of lipid rafts in the membrane of living cells.

Lipid Domain Structure of the Plasma Membrane Revealed by Patching of Membrane Components

The data strongly suggest that coalescence of cross-linked raft elements is mediated by their common lipid environments, whereas separation of raft and non-raft patches is caused by the immiscibility of different lipid phases, supported by the finding that cholesterol depletion abrogated segregation.

Crosslinking a lipid raft component triggers liquid ordered-liquid disordered phase separation in model plasma membranes.

This work investigates the large-scale physical effect of crosslinking a minor membrane component, the ganglioside GM1, in simple lipid models of the plasma membrane containing sphingomyelin, cholesterol, and phosphatidylcholine, and finds that this lipid separation causes a dramatic redistribution of a transmembrane peptide, consistent with a raft model of membrane organization.

Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation.

It is reported here that highly dynamic nanodomains exist in both the outer and inner leaflets of the plasma membrane and it is demonstrated that rafts are critically involved in the activation of a signaling axis that is essential for cell physiology.

Segregation of sphingolipids and sterols during formation of secretory vesicles at the trans-Golgi network

An immunoisolation procedure for specific recovery of post-Golgi secretory vesicles transporting a transmembrane raft protein from the TGN to the cell surface in the yeast Saccharomyces cerevisiae is devised and it is demonstrated that TGN sorting selectively enriched ergosterol and sphingolipid species in the immunoisolated secretoryVesicles.

Plasma membranes are poised for activation of raft phase coalescence at physiological temperature

It is demonstrated that raft clustering, i.e., amplifying underlying raft-based connectivity to a larger scale, makes an analogous capacity accessible at 37°C, and suggests that plasma membrane composition is poised for selective and functional raft clustered at physiologically relevant temperature.

Large-scale fluid/fluid phase separation of proteins and lipids in giant plasma membrane vesicles

It is demonstrated that giant plasma membrane vesicles (GPMVs) or blebs formed from the plasma membranes of cultured mammalian cells can also segregate into micrometer-scale fluid phase domains, and GPMVs now provide an effective approach to characterize biological membrane heterogeneities.