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NEW SPIN ON SPINDLE SIZE

A normal spindle (left) contrasts with frizzy ones from cells lacking TPX2 (right).

Like bridges and extension cords, the spindle that helps separate chromosomes during mitosis has to be the right length. Bird and Hyman show that two interacting proteins help set the spindle's dimensions.

When a cell builds a spindle, microtubules extend from several locations, including the chromosomes and the centrosomes. One mystery about the process is how cells dictate spindle length. A protein that might be involved is Aurora A, which promotes microtubule growth and is necessary for spindle formation. Another protein, TPX2, switches on Aurora A and helps position it on the spindle. By preventing TPX2 from activating Aurora A, Bird and Hyman tested whether this pair helps determine spindle length in human cells.

The standard way to address the question would be to add the gene for a defective version of TPX2, along with a viral promoter that controls its activity. However, previous work has shown that this method impairs mitosis. Instead, the researchers incorporated the mutant gene into a bacterial artificial chromosome that also harbored the gene's normal regulatory sequences. Inserted into a cell, this combination produces a more realistic pattern of gene activity, the scientists say.

When the scientists blocked Aurora A activation in this way, a squat spindle resulted. Although the cells could divide, mitosis often went awry, and they sometimes split into three daughter cells. With TPX2 unable to switch on Aurora A, microtubules that sprouted early in mitosis were unstable, the researchers found. Moreover, although microtubules extended from the centrosomes without Aurora A, they didn't grow from chromosomes. That result raises the possibility that Aurora A determines spindle size by spurring elongation of microtubules from the chromosomes. The researchers now want to determine what proteins Aurora A turns on to exert its effect.

Bird, A.W., and A.A. Hyman. 2008. J. Cell Biol. doi:10.1083/jcb.200802005.[Abstract/Free Full Text]

Mitch Leslie

mitchleslie{at}comcast.net

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This Article Full Text (PDF, 837K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Leslie, M. Search for Related Content PubMed Articles by Leslie, M. Social Bookmarking                            What's this?