Cytokinesis: The Central Spindle Takes Center Stage (original) (raw)

The central spindle plays a key role in cytokinesis. Recent studies have shed new light on how assembly of the central spindle is regulated, and also support a role for both the central spindle and astral microtubules in cytokinesis in animal cells. How cells determine the plane of cell division is one of the longest studied and most debated questions of cell biology (see [1] for review). Classic experiments by Ray Rappaport [2] on echinoderm embryos suggested that overlapping astral microtubules, emanating from the spindle poles, transmit a signal to the cell cortex to initiate furrowing. Other experiments, however, suggested that the signal to initiate furrowing comes from a structure called the spindle midzone, or the central spindle, particularly in smaller cells. A wide variety of more recent evidence strongly implicates the central spindle in cytokinesis. I will focus here largely on the central spindle, but will also discuss recent experiments that revive a role for astral microtubules in cytokinesis. When chromosomes begin moving to the spindle poles along kinetochore microtubules, the central spindle forms as a dense bundle of antiparallel nonkinetochore microtubules in the middle of the spindle. A number of proteins have been identified where loss of function disrupts both central spindle organization and cytokinesis. These include: the chromosomal passenger proteins INCENP, survivin, Aurora B kinase, and Borealin, the microtubule bundling protein PRC1, the kinesin MKLP1, and its associated Rho family GAP CYK-4 (reviewed in [3,4]). The various aliases of these proteins in different organisms are given in Table 1. Several new papers report results which have begun to shed light on how the timing of central spindle assembly is regulated. Earlier studies showed that formation of the central spindle is regulated by cyclin-dependent kinase (Cdk) activity. The central spindle begins to form at anaphase onset, when Cdk activity drops due to cyclin destruction. In fact expression of a nondestructible cyclin blocks central spindle formation and localization of Aurora B to the spindle, even though anaphase initiates normally [5,6]. Cdk regulation of central spindle formation seems to be mediated at least in part by direct phosphorylation of central spindle components (Figure 1). It has previously been shown that, in mammalian cells, the microtubule bundling protein PRC1 is a target of Cdk1 [7], and that Cdk phosphorylation seems to