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Harnessing actin dynamics for clathrin-mediated endocytosis

Nature Reviews Molecular Cell Biology volume 7, pages 404–414 (2006)Cite this article

Key Points

  • Several lines of evidence have implicated the actin cytoskeleton in the internalization step of clathrin-mediated endocytosis in various organisms from yeast to mammals.

  • Live-cell imaging studies have recently revealed a regular sequence of protein assembly events at endocytic sites. Actin and actin-cytoskeleton proteins are recruited to endocytic sites transiently during the budding of clathrin-coated endocytic vesicles.

  • Functional assays indicate that actin might be required for steps such as the invagination of the plasma membrane, the constriction of the vesicle neck and the scission of the endocytic vesicle.

  • Actin polymerization might provide the force for endocytic internalization. Proteins that link the growing actin-filament network to the endocytic coat might be used to harness the force of actin polymerization for vesicle budding.

  • The actin-related protein-2/3 (Arp2/3) complex nucleates actin-filament polymerization at endocytic sites and is a key target of many regulatory proteins. In Saccharomyces cerevisiae, in which the most extensive functional studies have been carried out so far, the activity of the Arp2/3 complex at endocytic sites seems to be tightly controlled by both positive and negative regulators.

  • Actin machinery that is similar to that used at endocytic sites is also used for the protrusion of lamellipodia. The same molecular machinery has therefore been adapted for different uses over the course of evolution.

Abstract

Actin polymerization often occurs at the plasma membrane to drive the protrusion of lamellipodia and filopodia at the leading edge of migrating cells. A role for actin polymerization in another cellular process that involves the reshaping of the plasma membrane — namely endocytosis — has recently been established. Live-cell imaging studies are shedding light on the order and timing of the molecular events and mechanisms of actin function during endocytosis.

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Figure 1: Actin-polymerization-driven processes in eukaryotic cells.
Figure 2: The sequential assembly of proteins at endocytic sites.
Figure 3: Modelling actin-driven endocytic internalization.
Figure 4: Current model for actin-driven endocytic internalization.

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Acknowledgements

We thank Y. Sun and V. Okreglak for critically reading the manuscript. Work in the laboratory of D.G.D. is supported by grants from the National Institutes of Health.

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  1. Department of Molecular and Cell Biology, University of California, Berkeley, 94720-3202, California, USA

    Marko Kaksonen, Christopher P. Toret & David G. Drubin

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  1. Marko Kaksonen
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  2. Christopher P. Toret
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  3. David G. Drubin
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Correspondence to David G. Drubin.

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Glossary

Lamellipodia

Sheet-like plasma-membrane protrusions at the leading edge of motile cells that are formed by actin polymerization.

Filopodia

Plasma-membrane spikes that are formed by actin polymerization.

Phagocytosis

A plasma-membrane-associated process in which a eukaryotic cell engulfs large particles, such as bacteria.

Macropinocytosis

A form of endocytosis in which extracellular fluid is taken up through the formation of large membrane vesicles.

Clathrin-mediated endocytosis

The uptake of receptors, membrane and cargo at the cell surface through a process that specifically involves the coat protein clathrin.

Caveolae-mediated endocytosis

A form of uptake at the plasma membrane that involves the protein caveolin.

Cofilin

A conserved actin-binding protein that is thought to be involved in actin-filament severing and disassembly.

Lucifer yellow

A fluorescent dye that enters cells by endocytosis and is often used as a marker for bulk endocytic uptake.

Arp2/3 complex

A protein complex that promotes the nucleation of actin filaments and creates a branched actin meshwork.

Formin-family proteins

A family of proteins that contain a formin homology-2 domain and can promote actin-filament assembly.

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Kaksonen, M., Toret, C. & Drubin, D. Harnessing actin dynamics for clathrin-mediated endocytosis. Nat Rev Mol Cell Biol 7, 404–414 (2006). https://doi.org/10.1038/nrm1940

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