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Tether and trap: regulation of membrane-raft dynamics by actin-binding proteins

Nature Reviews Immunology volume 7, pages 889–896 (2007)Cite this article

An Erratum to this article was published on 01 December 2007

Key Points

  • Although membrane rafts have often been studied using suboptimal or even improper approaches, recent studies have provided evidence in favour of a lipid compartmentalization of the plasma membrane. This was achieved either using novel and/or better-controlled techniques to visualize nanoscale molecular interactions in resting cells, or by analysing the complex membrane rearrangements that occur in an activated lymphocyte.

  • Lymphocyte migration and activation require the compartmentalization of membrane receptors and signalling molecules in specific cell locations, a process termed polarization. Cell polarization is accompanied by rapid cytoskeletal rearrangements and, at the plasma membrane, by the assembly of membrane rafts.

  • Membrane rafts have been implicated in the organization of signalling platforms that are required for the amplification of signal transduction during lymphocyte migration and activation. Interestingly, membrane-raft dynamics are controlled by co-stimulatory molecules in both B and T cells.

  • The actin cytoskeleton controls membrane-raft dynamics. By tethering and trapping membrane microdomains, the actin network influences the stability and the dimensions of membrane rafts and allows their concentration in active sites of the cell.

Abstract

The existence of plasma-membrane-raft microdomains has been widely debated during the past few years. However, it is clear that during lymphocyte stimulation a lipid-based reorganization occurs at the plasma membrane, with markers of the membrane rafts being selectively recruited to key active regions of the cell. Recent reports have demonstrated that membrane-raft dynamics are controlled by proteins that are linked to the actin cytoskeleton and have suggested a new model for the plasma membrane based on protein–lipid interactions. This new and dynamic view of the plasma membrane may improve our understanding of the complex process leading to cell polarization during lymphocyte migration and activation.

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Figure 1: The plasma membrane.
Figure 2: Possible roles of membrane rafts in cell migration.
Figure 3: Regulation of membrane-raft dynamics by actin-binding proteins.

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Acknowledgements

We thank M. Necci for assistance with original graphics and our colleagues for discussions. N.G. is the recipient of a K01 mentored research career development award (DK068,292) from NIDDK. A.V. is supported by grants from the Italian Association for Cancer Research (AIRC), MIUR/COFIN, the Cancer Research Institute of New York, the Department of Defense Prostate Cancer Research Program and the EMBO Young Investigator Programme. We apologize to colleagues whose work is cited via review rather than original work owing to space restraints.

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  1. Istituto Clinico Humanitas IRCCS, Via Manzoni 113, 20089 Rozzano, Milan, Italy

    Antonella Viola

  2. University of Milan, Faculty of Medicine, Italy

    Antonella Viola

  3. Department of Immunology, Cleveland Clinic, 9500 Euclid Avenue, NE40, 44195, Ohio, Cleveland, USA

    Neetu Gupta

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Glossary

Membrane rafts

Small (10–200 nm in diameter), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that can sometimes be stabilized to form larger platforms through protein–protein and protein–lipid interactions. Considering the new definition and the recent literature, the term 'membrane rafts' is preferable to 'lipid rafts'.

Detergent-resistant membranes

(DRMs). The low-density fractions obtained after the sucrose density gradient ultracentrifugation of detergent-lysed cells. In general, a neutral detergent solution at 4°C is used. The term DRM is not synonymous with membrane raft.

Lipid miscibility

The property of different lipids to mix and form homogeneous lipid phases. Sphingolipid–cholesterol rafts are considered to be liquid-ordered-phase domains that are dispersed in a liquid crystalline bilayer.

Membrane potential

The electrical-potential difference (voltage) across a cell's plasma membrane, which arises from the separation of positive and negative charges across the membrane owing to the action of ion transporters that maintain controlled ion concentrations inside the cell.

Fluorescence resonance energy transfer

(FRET). A quantum mechanical process by which excitation energy is transferred, without the emission of a photon, from a donor fluorophore to an acceptor fluorophore that is in close proximity. FRET can be used to analyse molecular interactions (in the range of 10–100 Å).

Immunological synapse

The specialized contact area between a T cell and one or more antigen-presenting cells, which is dynamic, and shows lipid and protein segregation, signalling compartmentalization and bidirectional information exchange through soluble and membrane-bound transmitters.

B-cell receptor capping

The binding of multivalent ligands to B-cell receptors induces redistribution and aggregation of the bound receptors into patches. Capping, which requires metabolic energy and cytoskeleton dynamics, represents the coalescence of patches to form a single aggregate called cap.

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Viola, A., Gupta, N. Tether and trap: regulation of membrane-raft dynamics by actin-binding proteins. Nat Rev Immunol 7, 889–896 (2007). https://doi.org/10.1038/nri2193

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