Lipid rafts: contentious only from simplistic standpoints

John F. Hancock, Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Australia. ua.ude.qu.bmi@kcocnah.j;

Abstract

The hypothesis that lipid rafts exist in plasma membranes and have crucial biological functions remains controversial. The lateral heterogeneity of proteins in the plasma membrane is undisputed, but the contribution of cholesterol-dependent lipid assemblies to this complex, non-random organization promotes vigorous debate. In the light of recent studies with model membranes, computational modelling and innovative cell biology, I propose an updated model of lipid rafts that readily accommodates diverse views on plasma-membrane micro-organization.

Abstract

A widely accepted hypothesis in contemporary cell biology is that freely diffusing, stable, lateral assemblies of sphingolipids and cholesterol, which are termed lipid rafts¹3, constitute an important organizing principle for the plasma membrane. The basic concept is that lipid rafts can facilitate selective protein–protein interactions by selectively excluding or including proteins. This lipid-based sorting mechanism has been widely implicated in the assembly of transient signalling platforms and more permanent structures such as the immunological synapse, as well as in the sorting of proteins for entry into specific exocytic and endocytic trafficking pathways¹3. Despite the undoubted theoretical utility of lipid rafts to many cell biological processes, the basic hypothesis that stable lipid rafts exist at all in biological membranes is under intense scrutiny⁴5. This is partly because lipid rafts, if they exist in resting cell membranes, are too small to be resolved by fluorescent microscopy and have no defined ultrastructure; therefore, proving their existence is problematic.

This article will consider the biophysical properties of model membranes that underpin the lipid raft hypothesis, and the limitations of the biochemical approaches that have been used to study rafts in biological membranes that largely account for the current debate on the hypothesis mentioned above. After examining the challenges that are involved in correlating observations, which have been made in model and cellular membranes, I focus on synthesizing recent data on the size of lipid domains in model membranes with observations that have been obtained by imaging intact plasma membranes. These imaging approaches include single particle tracking (SPT), single fluorophore video tracking (SFVT), fluorescence resonance energy transfer (FRET), homo-FRET and electron microscopy (EM). On the one hand, these studies challenge the simplistic null hypothesis that lipid-based assemblies, such as lipid rafts, do not exist in biological membranes. On the other hand, it is timely to reconsider the raft hypothesis in the light of these new data because the consensus model that emerges is more complex than a simplistic notion of stable, freely diffusing lipid rafts. Some intriguing new questions about the structure and function of lipid rafts in the plasma membrane, which are posed by this revised raft model, will be discussed.

Footnotes

Competing interests statement The author declares no competing financial interests.

DATABASES

The following terms in this article are linked online to: UniProtKB:http://ca.expasy.org/sprot

CD2 ∣ H-Ras ∣ LAT ∣ LCK ∣ Lyn ∣ MARCKS ∣ N-Ras ∣ PLAP ∣ THY1

FURTHER INFORMATION

John Hancock’s homepage: http://www.imb.uq.edu.au/index.html?id=11726

Access to this Links box is available online.

Footnotes

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