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Aug. 11, 2006 Research Highlight Biology

Placement of a new piece of the puzzle of cell division

Mud, an evolutionarily conserved protein, links cell polarity with cell division

Image of Mud localization in Drosophila neuroblasts Figure 1: Mud localization (red) regulates the orientation of mitotic spindles (green) in asymmetrically dividing wild-type Drosophila neuroblasts, or cells generating daughter cells that mature into nerve cells. DNA is blue.

Some cell types divide symmetrically, bestowing their contents equally upon two progeny. Other cell types divide asymmetrically, giving rise to two progeny that inherit unequal portions of parental cellular content. The choice of symmetry versus asymmetry is determined by the polarity of the cell, which influences the intracellular distribution of proteins, and by the position of the mitotic spindle, which effectively draws a line of division across a cell. Importantly, asymmetrical cell division is hardly the result of imprecision. In fact, the development of many biological systems, such as the neural system, depends on asymmetrical division. There are even indications that loss of asymmetry during cell division can result in a cancer-like state.

Previous work demonstrated that two Drosophila proteins, called Gαi and Pins, influence cell polarity and the position of the mitotic spindle. However, the mechanism by which Gαi and Pins regulate the cell division machinery was not completely understood. To tackle this question, Fumio Matsuzaki and colleagues at RIKEN’s Center for Developmental Biology in Kobe searched for proteins linking Pins to the mitotic spindle, and identified the Mushroom body defect (Mud) protein as a Pin-interacting factor. Their work is reported in Nature Cell Biology 1.

Images of dividing cells revealed that the cellular pattern of Mud localization correlates with the position of the mitotic spindle (Fig. 1). Analysis of cells lacking Pins demonstrated that Mud localization is influenced by Pins, and by components of the mitotic spindle itself. In cells expressing mutant forms of Mud, cell polarity was preserved, but mitotic spindle positioning was awry. These results highlight Mud as a factor essential for coupling cell polarity with mitotic spindle orientation. “This is the first time anyone has been able to show a general mechanism behind the coupling of cell polarity and axis of division,” says Matsuzaki. Interestingly, Mud was required for mitotic spindle positioning in both symmetrically and asymmetrically dividing cell types.

The importance of the Drosophila Mud protein is suggested by its extensive evolutionary conservation. Both vertebrates and earthworms express Mud homologues, which interact with Pins homologues. Precisely how Mud couples cell polarity to mitotic spindle orientation remains to be investigated. However, these findings “may help us develop new insights into the means by which cells switch between proliferative and differentiative modes of division”, notes Matsuzaki.

References

  • 1. Izumi, Y., Ohta, N., Hisata, K., Raabi, T. & Matsuzaki, F. Drosophila Pins-binding protein regulates spindle-polarity coupling and centrosome organization. Nature Cell Biology advance online publication, 30 April 2006. doi: 10.1038/ncb1409

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