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  • Review Article
  • Published:

Powering membrane traffic in endocytosis and recycling

Nature Reviews Molecular Cell Biology volume 7, pages 897–908 (2006)Cite this article

Key Points

  • Endocytic trafficking and subsequent recycling of plasma-membrane components is essential for cell viability. They direct the movement of vesicular carriers from the cell surface to the cell interior and back.

  • Endocytic uptake by phagocytosis or macropinocytosis requires different myosin motors that participate in the extension and closure of phagocytic cup pseudopods and their initial transport.

  • Clathrin-mediated endocytosis is tightly linked to the activity of the plus-end directed motor myosin VI, whereas an involvement of a motor(s) in caveolar endocytosis is unclear at present.

  • Microtubule-dependent, minus-end-directed transport definitely requires dynein and its activator, dynactin. The participation of a minus-end-directed kinesin has been suspected, but not proven conclusively.

  • Plus-end-directed motors from several kinesin families also participate in endosomal trafficking along microtubules, leading to prominent bidirectional movement of early and late endosomes as well as lysosomes.

  • Recycling can occur through several pathways, possibly starting at the early endosome step, and requires plus-end-directed microtubule transport. Depending on the cargo in question, transport is powered by members of the kinesin-1, -2 and -3 families.

  • A prominent motor class that is involved in the final steps of delivery to the cell surface is myosin V, although class-I myosins also operate primarily in the cell cortex near the plasma membrane.

  • The cooperation between microtubule and actin motors entails control by small G-proteins and other regulators. Different motors and their regulators can thereby form a complex on the surfaces of trafficking organelles, although this is hypothetical at present.

Abstract

Early in evolution, the diversification of membrane-bound compartments that characterize eukaryotic cells was accompanied by the elaboration of molecular machineries that mediate intercompartmental communication and deliver materials to specific destinations. Molecular motors that move on tracks of actin filaments or microtubules mediate the movement of organelles and transport between compartments. The subjects of this review are the motors that power the transport steps along the endocytic and recycling pathways, their modes of attachment to cargo and their regulation.

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Figure 1: The structural diversity of molecular motors.
Figure 2: Overview of the motors that are involved in endocytic and recycling traffic.

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Acknowledgements

Research is supported by grants from the UK Biotechnology and Biological Sciences Research Council, the Wellcome Trust and the Swiss National Science Foundation to T.S., and the Deutsche Forschungsgemeinschaft, the Friedrich–Baur–Stiftung and the Fonds der Chemischen Industrie to M.S. Owing to space limitations, not all of the relevant references could be cited.

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  1. Départment de Biochimie, Faculté des Sciences, Université de Genève, 30 quai Ernest Ansermet, Sciences II, Genève, 4, CH-1211, Switzerland

    Thierry Soldati

  2. Institute for Cell Biology, University of Munich, Schillerstr. 42, Munich, D-80336, Germany

    Manfred Schliwa

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Glossary

Endocytosis

A plasma-membrane-associated process in which a eukaryotic cell engulfs extracellular fluid or particles.

Phagocytosis

A form of endocytosis in which a eukaryotic cell engulfs large particles, such as bacteria.

Pinocytosis

A form of endocytosis in which a eukaryotic cell engulfs extracellular fluid and solutes.

Macropinocytosis

A form of pinocytosis, morphologically and mechanistically related to phagocytosis, by which cells form large membrane vesicles.

Clathrin-mediated endocytosis

A form of pinocytosis, often also referred to as receptor-mediated endocytosis, in which the invagination of the endocytic vesicle is driven by the clathrin coat.

Caveolae-mediated endocytosis

A form of pinocytosis that is driven by a coat made of the protein caveolin.

Clathrin- and caveolae-independent endocytosis

A form (or forms) of uptake that is revealed when the two other endocytosis pathways are blocked.

Lamellipodia

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

Phagocytic cup

A bowl-shaped lamellipodia-like protrusion that forms around particles during phagocytic uptake.

Processivity

The capability of a single motor to move for long distances without dissociating from the track.

Acanthamoeba

A genus of small, highly motile soil amoebae that are frequently used for studies of actin-binding proteins and cell locomotion. Some pathogenic forms are known.

Minus end (plus end) direction

Both actin filaments and microtubules demonstrate polarity, and are assembled from monomers that are added at a high rate at one end (the plus end) and at a much slower rate at the other (the minus end). Motors can transport cargo in either direction, processes that are referred to as plus-end-directed and minus-end-directed transport.

Snell's waltzer phenotype

A mouse mutation in myosin VI that arose spontaneously at the Jackson laboratory in the 1960s. It affects inner ear structure and leads to deafness and vestibular dysfunction, causing the mice to circle.

Caveosomes

Endocytic vesicles enriched for the protein caveolin-1 formed from caveolae, flask-shaped pits in the membrane that resemble a cave.

RAB

One family of the large superfamily of small GTP-binding proteins involved in a myriad of cellular functions. RAB proteins are best known for their role in the timing of vesicle fusion.

Actin comet tail

A network of actin filaments that is assembled from one end of an intracellular bacterium (such as Listeria or Shigella) or a cytoplasmic vesicle and that takes on the form of a comet tail. Constant actin polymerization at the surface pushes the bacteria or vesicles through the cytoplasm.

Melanophore

A class of pigment-containing cell that is responsible for the generation of skin and eye colour. The pigment melanin (a tyrosine-polymer) is concentrated in vesicles (melanosomes) that can be translocated in the cell, causing colour change.

Cell cortex

The zone of the cell periphery, directly under the plasma membrane, where the actin cytoskeleton forms a dense meshwork.

CLIP

(Cytoplasmic linker protein). These were originally thought to load endocytic vesicles onto the plus ends of microtubules. CLIPs are part of the microtubule-plus-end-tracking complex (+TIPs) and are associated with the distal ends of microtubules.

Hyphal apex

Hyphae are long, branching filaments that are mostly found in the fungi that form the mycelium, the vegetative network below the ground. Hyphae only grow at the tip, and the hyphal apex contains a growth-related vesicular organelle cluster called Spitzenkörper (tip body).

Rigor mutant

A dominant-negative mutation of the ATP-binding domain in a motor that locks it irreversibly to its cytoskeletal partner.

Syntaxin-1a

A form of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein with a single transmembrane domain that participates in exocytosis. Its C-terminal domain is part of the core SNARE complex, which mediates membrane fusion.

Astrocytes

Star-shaped glial cells in the brain that interact with neurons in multiple ways. They are identified by the expression of glial fibrillary acidic protein (a type of intermediate filament protein) and they outnumber neurons ten to one.

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Soldati, T., Schliwa, M. Powering membrane traffic in endocytosis and recycling. Nat Rev Mol Cell Biol 7, 897–908 (2006). https://doi.org/10.1038/nrm2060

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