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A minus end checkpoint

Abormal spindles and mitotic stalls occur upon depletion of the -TuRC proteins Grip71 and -tubulin, but not the centrosomal structural protein cnn. LANGE/AAAS

Both ends of microtubules get in on spindle checkpoint signaling. From kinetochores, proteins at microtubule plus ends relay the results of proper spindle-to-chromosome attachments. Now, Hannah Müller, Bodo Lange (Max Planck Institute for Molecular Genetics, Berlin, Germany), and colleagues find that, at minus ends, -tubulin signals that all is well with microtubule nucleation.

Spindle microtubule minus ends are focused at the centrosome, where the microtubule-nucleating -tubulin ring complex (-TuRC) resides. Müller et al. found that the loss of -TuRC proteins, including -tubulin, activates the spindle checkpoint. The problem does not seem to stem from fewer spindle-to-kinetochore attachments, as spindle microtubule density was not strongly reduced.

The group instead finds a connection between -TuRC and known spindle assembly checkpoint proteins. Both Cdc20 and BubR1 copurified with -tubulin in human and fly cell extracts. Loss of a functional checkpoint, via knockdown of BubR1 for example, overcame the mitotic stall caused by -tubulin loss.

The arrest could not, however, be overcome by disrupting centrosomes. Thus the checkpoint relies on -TuRC for microtubule nucleation, but the centrosome as a "molecular hub" is not required for this particular process.

Reference:

Müller, H., et al. 2006. Science. 314:654–657.[Abstract/Free Full Text]

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article Full Text (PDF, 845K) 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 LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?