Molecular motors and their role in membrane traffic

doi:10.1016/S0169-409X(97)00081-1

Advanced Drug Delivery Reviews

Volume 29, Issue 3, 2 February 1998, Pages 229-242

https://doi.org/10.1016/S0169-409X(97)00081-1 Get rights and content

Abstract

Recent investigations support a role for the vesicle motor proteins (kinesin, cytoplasmic dynein, and myosin) in numerous membrane trafficking events including endocytosis and transcytosis. Kinesin and cytoplasmic dynein are responsible for movement of membrane vesicles along cellular microtubules to and from cellular membrane compartments, while certain members of the myosin family also appear to drive membrane vesicles along actin filaments to and from membrane compartments. In this review, our current understanding of the role of these vesicle motors in membrane trafficking is highlighted. Future areas of interest which may be able to make use of these vesicle motors as potential targets for drug delivery are also discussed.

Introduction

Many recent advances in targeted drug delivery have focused on regulation of the endogenous membrane trafficking machinery in order to facilitate uptake of polar drugs via receptor-mediated endocytosis into target tissues. To truly enhance drug delivery, it is necessary to have a complete understanding of the events involved in the movement of surface-bound and extracellular components by endocytosis into the cell. It is equally important to have a complete understanding of the events involved in sorting of the internalized complex. For instance, if internalization of the drug is immediately followed by its recycling, then no accumulation can occur. Similarly, if internalization of the drug is immediately followed by its transport to a lysosomal compartment leading to degradation of drug, then no accumulation can occur. Therefore, the best strategies for enhancing drug delivery to a target organ will focus not only on endocytosis but on regulation of sorting events within the endocytic pathways that govern the intracellular destination and ultimately the fate and persistence of the drug.

An important component of traffic within the endocytic pathway is the process of vesicle transport. This review will focus primarily on the vesicle transport that is driven by the microtubule (MT)-based motor proteins, kinesin and cytoplasmic dynein, along the cytoskeletal MT network. The role of kinesin and cytoplasmic dynein in facilitating vesicle transport in a variety of membrane trafficking events will be reviewed. Although the actin-based motor protein, myosin, is more often considered within the context of force generation leading to the energy-driven sliding of actin filaments to produce contractile force, recent studies have shown that some members of the myosin superfamily drive vesicle transport along actin-based microfilaments (MFs). Our current understanding of the role of myosin-driven vesicle transport in membrane trafficking will also be briefly reviewed and the possible interrelationships between the MF-based and MT-based vesicle transport systems will be discussed. Finally, the relevance of these vesicle motors to the field of drug delivery will be highlighted.

Section snippets

Cytoskeletal structures which support vesicle movements

Cellular MTs are polar cytoskeletal polymers consisting of protofilaments formed by head-to-tail association of two globular proteins of 53–55 kD, α- and β-tubulin, to form a dimer and then a multimeric protofilament (reviewed in Refs. 1, 2). The ends of the MT are biochemically and functionally distinct and are referred to as plus- and minus-ends, which refers to their relative abilities to incorporate additional tubulin subunits in vitro. This polarity is quite important for MT function,

Conclusion

Membrane trafficking and endocytosis are highly complex processes which involve a number of different proteins. This review has focused on the role of the vesicle motor proteins which move along paths defined by MTs and MFs in membrane trafficking. Numerous proteins participate in membrane trafficking and endocytosis; however, changes in the MT array and in MT-based vesicle transport have previously been linked to corresponding changes in receptor-mediated endocytosis and intracellular sorting.

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Molecular motors and their role in membrane traffic

Abstract

Introduction

Section snippets

Cytoskeletal structures which support vesicle movements

Conclusion

Curr. Opin. Cell Biol.

Curr. Opin. Cell Biol.

Curr. Opin. Cell Biol.

Curr. Opin. Cell Biol.

Curr. Opin. Cell Biol.

Curr. Opin. Cell Biol.

Curr. Opin. Cell Biol.

Cell

Cell

Neuron

J. Biol. Chem.

Cell

J. Biol. Chem.

Exp. Eye Res.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Curr. Opin. Cell Biol.

J. Biol. Chem.

Curr. Opin. Cell Biol.

J. Biol. Chem.

Hepatology

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Microtubule dynamics: mechanism, regulation and function

Annu. Rev. Cell Biol.

Microtubules and microtubule-associated proteins

Curr. Opin. Cell Biol.

Microtubule-dependent motor proteins: new targets for drug delivery?

Pharm. Res.

Control of actin assembly at filament ends

Annu. Rev. Cell Dev. Biol.

Three-dimensional organization of rat hepatocyte cytoskeleton: relation to the asialoglycoprotein endocytosis pathway

J. Cell Sci.

The transcytotic pathway of an apical plasma membrane protein (B10) in hepatocytes is similar to that of IgA and occurs via a tubular pericentriolar compartment

J. Cell Sci.

Cytoplasmic microtubule-associated motors

Annu. Rev. Biochem.

Two activators of microtubule-based vesicle transport

J. Cell Biol.

Dynactin, a conserved, ubiquitously expressed component of an activator of vesicle motility mediated by cytoplasmic dynein

J. Cell Biol.

Homology of a 150K cytoplasmic dynein-associated polypeptide with the Drosophila gene Glued

Nature

A vertebrate actin-related protein is a component of a multisubunit complex involved in microtubule-based vesicle motility

Nature

Ultrastructural analysis of the dynactin complex: an actin-related protein is a component of a filament that resembles F-actin

J. Cell Biol.

Kinesin family in murine central nervous system

J. Cell Biol.

KIF3A is a new microtubule-based anterograde motor in the nerve axon

J. Cell Biol.