Despite its static-sounding name, the actin cytoskeleton is a dynamic structure. As eukaryotic cells progress through the cell cycle, for example, the cytoskeleton is remodelled, culminating in the formation of an actin ring that constricts during cytokinesis. The connection between these changes and the cell cycle has not been clear, but a report in Nature now describes a hitherto unknown mitotic checkpoint that specifically monitors the actin cytoskeleton.

This startling finding emerged when Gachet, Tournier and colleagues treated synchronized Schizosaccharomyces pombe cells with a drug that inhibits actin polymerization — latrunculin B — and found that these cells stopped during mitosis for upwards of an hour. Not only that but the orientation of the bipolar spindle, which is responsible for segregating the duplicated chromosomes, was disrupted in the treated cells. Given the spindle defect, the authors then asked whether latrunculin B has any effect on sister-chromatid separation. They observed a single signal from a fluorescently labelled marker for centromeres, indicating that the sister chromatids had not separated.

In fission yeast, sister chromatids are glued together by a protein called Rad21, and separate only when this protein is cleaved by a specialized protease known as Cut1 or separase. Cut1 is, in turn, activated by destruction of an inhibitory subunit called Cut 2 (securin), which is ubiquitylated — and targeted for destruction — by the anaphase-promoting complex (APC). Gachet et al. showed that, in the presence of latrunculin B, cleavage of Rad21 is delayed. However, destruction of Cut2 was unaffected by this treatment, indicating that disruption of the actin cytoskeleton delays sister-chromatid separation without affecting the APC. The authors also showed this checkpoint to be independent of the spindle-assembly checkpoint, which delays mitosis in response to a defective spindle or when chromosomes fail to attach to the spindle.

So what are the components of this new checkpoint? Gachet et al. screened for mutant cells that were more sensitive than wild-type cells to latrunculin B, and pulled out Atf1 (the yeast homologue of the human transcription factor ATF2) and Sty1/Spc1 (a mitogen-activated protein kinase). Both proteins belong to the stress-activated protein kinase pathway (SAPK), with Sty1/Spc1 phosphorylating — and hence activating — Atf1. (The figure shows wild-type cells (left) and Δatf1 cells (right) in the presence of latrunculin B.)

The authors conclude that the SAPK pathway is involved in controlling this actin-dependent mitotic checkpoint, which probably “ensures mitotic spindles are properly oriented before anaphase is allowed to take place”. This checkpoint might be especially important during the development of multicellular organisms, when the establishment of asymmetric cell fates can depend on the orientation of the spindle during mitosis.