Functional redundancy in mitotic force generation

HE pushing and pulling forces that characterize the rocess of mitosis have fascinated and frustrated biolo-ists for over a century. While considerable progress has been made in understanding how these forces are used in mitosis, the nature of the molecules that generate the forces has remained obscure., have demonstrated that members of the kinesin su-perfamily of microtubule motors are likely to generate some of these forces. Intriguingly, the functions of some of these molecules are nonessential. Coupled with recent demonstrations that dynein (Pfarr et al., 1990; Steuer et al., 1990) and microtubule depolymerization (Koshland et al., 1988; Coue et al., 1991) could also produce spindle forces, these observations raise the possibility that spindle force generation is a highly redundant process. Three of the most obvious mitotic movements and forces occur during prophase, metaphase, and anaphase (reviewed in McIntosh and Pfarr, 1991). First, during prophase, the newly duplicated spindle poles or centrosomes separate to form the bipolar mitotic spindle. Second, during anaphase, chromosomes move to the spindle poles as a result of pnlling forces generated between the chromosomes and the spindle poles. At metaphase, when chromosomes are aligned at the middle of the spindle, a similar force may also cause poles to be pulled towards one another (see Fig. 1). Third, also during anaphase, spindle poles separate from one another as the spindle elongates. This movement appears to be largely driven by forces intrinsic to the spindle that push the spindle poles apart. This force may also counterbalance the force generated between chromosomes and poles at metaphase, and thus keep the spindle from collapsing. All of these forces may, at least in part, be generated by members of the kinesin superfamily of proteins. The kinesin superfamily was defined by its founding member , the kinesin heavy chain, which is the principal component of the microtubule-dependent motor protein kinesin (Vale et al., 1985). This protein was first found in squid axo-plasm but was subsequently found to be virtually ubiquitous, which led to the view that kinesin itself might produce the force driving some of the various mitotic movements (reviewed in Sawin and Scholey, 1991). While this view could still have some validity, the bulk of recent evidence suggests that kinesin itself may not play a role in mitosis. Instead , a group of proteins distantly related to kinesin heavy chain, called kinesin-like proteins or kinesin-related proteins , appear to play key roles …