ScienceWeek

CELL BIOLOGY: ON THE CENTROSOME

The following points are made by Edward H. Hinchcliffe (Current Biology 2003 13:R646):

1) The key to a successful division of a eukaryotic cell is the assembly of a bipolar mitotic spindle: this allows all chromosomes to attach their kinetochores to opposite poles, and segregate quickly and equally into the two daughter cells. The bipolar spindle axis is ultimately determined by the duplication of the centrosome, an organelle that consists of a pair of centrioles -- mother and daughter -- surrounded by a matrix of pericentriolar material (1). If the centrosome duplicates more than once per cell cycle, the possibility that the cell will assemble a multipolar spindle and become aneuploid increases(2).

2) While the major function of the centrosome is to organize interphase microtubules, this network will self-organize in the absence of centrosomes(3). Of interest is that in the absence of centrosomes, the cell will also assemble a bipolar mitotic spindle, induced in the region of the chromosomes (4). While such findings have challenged the importance of the centrosome, the centrosome still appears to be the dominant microtubule-organizing center and spindle pole when present in a cell (5).

3) In addition to its role as microtubule-organizing center and spindle pole organizer, the centrosome is also required for the completion of cytokinesis, and cell-cycle progression in interphase. Removal of the centrosome, either by laser ablation or micro-surgery, does not prevent the cell from forming a bipolar spindle, but these cells -- termed karyoplasts -- exhibit defects in cytokinesis and cannot progress to the next S phase. Furthermore, mitosis in certain cells (BSC-1 karyoplasts) is significantly delayed compared to controls, with timing defects observed before and after anaphase onset, suggesting that the presence of a centrosome and/or astral microtubules is necessary to ensure timely mitotic progression. The results of these studies have revealed a role for the centrosome in cell cycle regulation, but not the molecular mechanisms underlying these functions.

References (abridged):

1. Steams, T. (2001). Centrosome duplication. A centriolar pas de deux. Cell 2001, 705,417-420

2. Brinkley, B.R. (2001). Managing the centrosome numbers game: from chaos to stability in cancer cell division. Trends Cell Biol. 2001, 77,18-21

3. McNiven, M.A., Wang, M., and Porter, K.R. (1984). Microtubule polarity and the direction of pigment transport reverse simultaneously in surgically severed melanophore arms. Cell 37, 753-765

4. Heald, R., and Weis, K. (2000). Spindles get the ran around. Trends Cell Biol. 70,1-4

5. Raff, J.W. (2001). Centrosomes: Central no more? Curr. Biol. 77, R159-R161

Current Biology http://www.current-biology.com

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ON THE CENTROSOME

The following points are made by C. Wong and T. Stearns (Current Biology 2003 13;R351):

1) The centrosome was first described in the late 1800s by Van Beneden and Boveri as a small body at the center of fibrous asters in invertebrate eggs. Although always of interest to cell biologists, research on the centrosome languished until the 1990s, when two advances brought the focus back to the centrosome. First, proteins of the centrosome began to be identified, bringing a molecular understanding to centrosome function. Second, a link between the centrosome and cancer was established by the observation that cancer cells often have centrosomes of aberrant size and number. Such a link was first proposed 90 years ago by T.H. Boveri (1862-1915), and there is great interest in determining the cause of these centrosome defects, and whether they are behind the genomic instability common in cancer cells.

2) What is the centrosome? A typical centrosome is approximately 1 cubic micron in volume and composed of a pair of centrioles surrounded by a matrix of pericentriolar material. The centrioles are among the most highly conserved structures in eukaryotic cells, consisting of a cylinder formed by microtubule structures arranged with perfect nine-fold symmetry. The pericentriolar material is known to contain several large coiled-coil proteins which make up the matrix, as well as the gamma-tubulin ring complex, which forms microtubule nucleation sites.

3) The centrosome has two remarkable properties that separate it from most other organelles. First, it duplicates precisely once per cell cycle, so that a constant number is maintained. Second, the centrosome is not membrane-bound, and yet differs from the surrounding cytoplasm. These properties raise three interesting questions: How does the centrosome duplicate? How are specific proteins recruited from the cytoplasm to form an assemblage around the centrioles? And how does the centrosome maintain a constant size?

Current Biology http://www.current-biology.com

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