Review
Membrane trafficking, organelle transport, and the cytoskeleton

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Abstract

Cytoskeleton-associated motor proteins typically drive organelle movements in eukaryotic cells in a manner that is tightly regulated, both spatially and temporally. In the past year, a novel organelle transport mechanism utilizing actin polymerization was described. Important advances were also made in the assignment of functions to several new motors and in our understanding of how motor proteins are regulated during organelle transport. In addition, insights were gained into how and why organelles are transported cooperatively along the microtubule and actin cytoskeletons, and into the importance of motor-mediated transport in the organization of the cytoskeleton itself.

Introduction

Intracellular transport of organelles is a fundamental process essential to many cellular functions. Most organelle movements are driven along microtubules and actin filaments by motor proteins. These fascinating proteins convert the chemical energy released by nucleotide hydrolysis directly into movement. These movements can be harnessed to effect gross changes in cellular shape, for example during muscle contraction, spindle elongation, cytokinesis, or cell migration. Alternatively, motors can be employed for intracellular transport of cargo, in processes such as chromosome segregation, centrosome positioning, placement of polarity determinants, mRNA transport, and trafficking of membranous organelles (for recent reviews see 1, 2). In this review, we focus upon the major developments in organelle transport and its regulation.

Section snippets

A novel mechanism of organelle transport

Certain intracellular pathogens, such as Listeria, Shigella, and some viruses, exploit their host-cell’s cytoskeleton for movement throughout the cytoplasm. The bacteria express proteins on their surface, which recruit actin filament nucleation factors from the host cell (reviewed in [3]). The result is a polarized burst of actin polymerization from one pole of the bacterium that propels it through the cell at the front of a characteristic ‘comet tail’ structure. Merrifield et al. [4••]

Identification of functional roles for motors in organelle transport

Possibly the most convincing assignments of motor function has resulted from studies in which motor proteins are inactivated genetically. For example, generation of mice bearing targeted gene knockouts for specific motors 5••, 6•, 7• and mutants isolated using traditional genetics in other organisms 8•, 9• have facilitated assignment of functional roles to several motors over the past year. Another fruitful approach has been transient transfection of cells with constructs that encode a

The microtubule and actin cytoskeletons act cooperatively to transport organelles

A dramatic example of this type of cooperative transport has resulted from the study of melanosome transport in dermal pigment cells. In melanophores — cells present in the skin of fish and frogs — melanosomes (pigment granules) either aggregate at the center of the cell or disperse en masse in response to a hormonal stimulus. The cumulative effect of this transport is to effect color change of the animal. Pigment-granule transport is known to occur bidirectionally along the radially-organized

Intracellular transport of cytoskeletal filaments

Microtubules participate in the organization of other components of the cytoskeleton, such as actin in the contractile ring of dividing cells, the actin network at the leading edge of migrating cells, and intermediate filaments in the cytoplasm. Recent work shows that, in at least some cases, this is achieved by direct transport of these cytoskeletal components along microtubules. Using in vitro assembled microtubule asters, Sider et al. [30••] demonstrated that filamentous actin bound in a

Regulation of organelle transport

Although the functions of many motors have been elucidated over the past several years, the molecular mechanisms governing motor activity and cargo attachment still remain largely unknown. Recently, important insights into motor regulation came from the study of conventional kinesin. Kinesin exists as a heterotetramer composed of two heavy chains and two light chains. The heavy chains have a tripartite structure: an amino-terminal head, which contains the catalytic motor domain, a central stalk

Conclusions

Seminal discoveries have been made in the field of organelle transport over the past several years, yet it is clear that much work remains to be done. Although conventional kinesin was first identified over a decade ago the molecular mechanisms governing its regulation are only now being elucidated. We do not know if other members of the kinesin motor protein superfamily exhibit similar regulatory mechanisms. Given the diversity of structural organization exhibited by the kinesins, this is

Acknowledgements

We would like to thank Amy Reilein for critical reading of the manuscript. Our research is supported by grants from National Science Foundation (MCB 95-13388) and National Institutes of Health (GM-52111).

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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