Formin' the Connection between Microtubules and the Cell Cortex

I n higher eukaryotes, the position of cytokinesis is determined by the position of the mitotic spindle (Rappaport, 1990). Generally, the spindle sits in the middle of the cell and cytokinesis produces two equivalent cells. However, many developmental processes require specific positioning of the cleavage plane and, hence, the mitotic spindle. For example, control of spindle position can be used to asymmetrically distribute cell fate determinants between the two daughter cells, to form polar bodies during oogenesis, and for tissue morphogenesis (Stearns, 1997). Positioning of the spindle appears to be mediated through the attachment of astral microtubules to filamentous actin at the cell cortex (Lutz et al., 1988; Hyman, 1989; Waddle et al., 1994). In budding yeast, the site of cell division is specified at the start of the cell cycle by the location of the bud site. The mitotic spindle must then be positioned in the neck between mother and bud to achieve segregation of chromosomes between the mother and daughter cells. Positioning the mitotic spindle in yeast involves three processes (Fig. 1, Table I). Before mitotic spindle formation, a kinesin, Kip3p, is required for movement of the nucleus to the mother-bud neck (DeZwaan et al., 1997). After spindle formation, Kip3p is needed to orient the pre-anaphase spindle along the mother bud axis. Dynein functions later in mitosis to move the anaphase spindle into the neck (Stearns, 1997). How Kip3p and dynein function in these movements is not known. They may pull on microtubules in the traditional sense of a motor, or they may regulate microtubule length via effects on dynamic instability at microtubule ends. Astral microtubules are highly dynamic and occasionally span the distance from the spindle pole body to the cell cortex (Shaw et al., 1997). Therefore, spindle movements are hypothesized to depend on transient, short-lived interactions between astral microtubules and the cell cortex. Two papers in this issue of the Journal define components involved in microtubule-cortex interactions during the early spindle movements that require Kip3p (Lee et al., 1999; Miller et al., 1999). Lee and colleagues and Miller and colleagues found that Bni1p, a formin, and Bud6p participate in movement of the nucleus to the bud neck and in orienting the preanaphase spindle (Lee et al., 1999; Miller et al., 1999). Formins control actin-dependent processes in many systems (Frazier and Field, 1997). The new results showing that Bni1p and actin are necessary for spindle positioning suggest that microtubules interact with actin at the cell cortex. The localization of Kar9p, another protein involved in Kip3p-dependent movements, depends on actin, Bni1p and Bud6p (Miller et al., 1999).