Review Article | Published:

Re-evaluating centrosome function

Nature Reviews Molecular Cell Biology volume 2, pages 688698 (2001) | Download Citation

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Abstract

Over the past 100 years, the centrosome has risen in status from an enigmatic organelle, located at the focus of microtubules, to a key player in cell-cycle progression and cellular control. A growing body of evidence indicates that centrosomes might not be essential for spindle assembly, whereas recent data indicate that they might be important for initiating S phase and completing cytokinesis. Molecules that regulate centrosome duplication have been identified, and the expanding list of intriguing centrosome-anchored activities, the functions of which have yet to be determined, promises continued discovery.

Key points

  • In most vertebrate cells, centrosomes consist mainly of two substructures — centrioles and pericentriolar material. The pericentriolar material, a meshwork of fibres and protein aggregates, seems to be the site of microtubule nucleation. The exact function of centrioles is unclear, but they may mediate the recruitment and organization of centrosome components.

  • Centrosomes are the main site of microtubule nucleation in most cells. Different types of molecules are thought to mediate microtubule nucleation, anchoring and finally, release.

  • Many centrosome proteins undergo cell-cycle-regulated assembly onto centrosomes. Both dynein-dependent and -independent pathways may act redundantly to mediate centrosome assembly, with different pathways dominanting in different cell types or at different times during the cell cycle or development.

  • Although it now appears that centrosomes are not strictly required for bipolar spindle assembly, centrosome-mediated assembly is likely to be an important redundant pathway that ensures high fidelty of chromosome segregation.

  • New roles for centrosomes are now emerging. These include positioning the mitotic spindle, the completion of cytokinesis, G1 to S progression, and initiation DNA replication. Centrosomes might also have a role in coordinating actin poymerization during pseudocleavage in Drosophila — a role that seems to be independent of microtubules and suggests that centrosomes might act as diffusion centres for signalling molecules.

  • Centrosome duplication occurs once per cell cycle, and is tightly coordinated with events such as cell-cycle progression and DNA replication. The molecular pathway that controls duplication is now being revealed, and includes both cell-cycle regulators and downstream factors such as nucleophosmin, the degradation of which may be required for centriole splitting.

  • Centrosomes act as anchoring sites for regulators of diverse cellular functions. The significance of this association and how these factors communicate with the rest of the cell is an area of great interest.

  • Because both centrosomes and acentriolar microtubule-organizing centres organize dysfunctional mitotic spindles, both have the potential to contribute to genetic instability during tumorigenesis. However, a driect link between centrosomes and cancer has not yet been established.

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Acknowledgements

I apologize to colleagues whose work is not discussed or cited owing to space constraints. I would like to thank K. Sluder, B. Theurkauf, F. McNally and D. McCollum for critical reading of the manuscript. S.D. is an American Heart Established Investigator and is supported by the National Institutes of Health, the National Cancer Institute and the Department of Defense.

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  1. Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, Massachusetts 01605, USA. stephen.doxsey@umassmed.edu

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Glossary

INTERPHASE

The period between two mitotic divisions.

CENTRIOLES

Open-ended cylinders, comprised of nine sets of triplet microtubules linked together and containing appendages on the outside and protein assemblies and sometimes vesicles on the inside. Centrosomes usually contain two centrioles.

MICROTUBULE

A hollow tube, 25 nm in diameter, formed by the lateral association of 13 protofilaments, which are themselves polymers of α- and β-tubulin subunits.

SPINDLE POLE BODY

The acentriolar microtubule-organizing centre of yeast and diatoms. It is a plaque-like structure that is embedded in the nuclear membrane that faces the cytoplasm on one side and the nuclear interior on the other.

COILED COIL

A protein domain that forms a bundle of two or three α-helices. Whereas short coiled-coil domains are involved in protein interactions, long coiled-coil domains forming long rods occur in structural or motor proteins.

PRIMARY CILIUM

A single, probably non-motile, cilium that grows from the maternal centriole of the centrosome in most cell types.

CYTOKINESIS

The process of cytoplasmic division.

MITOSIS

The process of nuclear division.

ASTER

A radial array of microtubules focused on and usually nucleated by centrosomes or aggregates of centrosome/spinlde pole proteins.

S VALUE

(Sedimentation coefficient.) A standardized value, describing migration of molecules/particles under a centrifugal force.

KINETOCHORE

A structure that connects each chromatid to the spindle microtubules, which shorten as pairs of chromatids are separated to opposite poles.

ANEUPLOIDY

Presence of extra copies, or no copies, of some chromosomes.

CHECKPOINT

A point where the cell division cycle can be halted until conditions are suitable for the cell to proceed to the next stage.

GUANINE-NUCLEOTIDE EXCHANGE FACTOR

A protein that facilitates the exchange of GDP (guanine diphosphate) for GTP (guanine triphosphate) in the nucleotide-binding pocket of a GTP-binding protein.

ORTHOLOGUE

Homologous genes in different species, the lineages of which derive from a common ancestral gene without gene duplication or horizontal transmission.

SCF COMPLEX

A multisubunit ubiquitin ligase that contains Skp1, a member of the cullin family (Cul1), and an F-box-containing protein (Skp2), as well as a RING-finger-containing protein (Roc1/Rbx1).

PROTEASOME

Large multisubunit protease complex that selectively degrades intracellular proteins. Targeting to proteasomes most often occurs through attachment of multi-ubiquitin tags.

MALD TOF

A method designed to determine peptide mass maps of very small amounts of enzymatically digested proteins with a very high degree of accuracy. Masses are determined by measuring peptides that are ionized in a vacuum.

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