Figure 2. Fundamental sliding filament mechanisms.

The orientation of cross-linked microtubules and the directional preference of the cross-linking motor dictate how sliding filament mechanisms contribute to spindle assembly and maintenance. In A, microtubules overlapped at their plus ends with an antiparallel orientation, which commonly occurs near the midzone of the spindle (see [20, 84, 85]), are pushed outward, toward the poles, by plus end-directed kinesin-5 motors. White arrows show the resulting direction of microtubule sliding. Conversely, minus end-directed motors such as dynein or kinesin-14 family members would act to pull the minus ends of the same microtubules together, sliding the microtubules inward, toward the spindle midzone ([20, 37]; B). A balance between these opposing forces is thought to contribute to achieving a steady-state spindle length. The other extreme of microtubule orientations is parallel alignment (C). In this geometry the effect of the motor on microtubule sliding depends on whether the motor “hangs on” once it reaches a microtubule end. A motor with bipolar symmetry like kinesin-5 would bind to and move processively along both the microtubules it cross-links without producing any relative sliding. In this way the motor may act to better align parallel microtubules along their lengths by “zippering” them up without sliding them [56]). For an asymmetric motor like dynein, which binds to microtubules via a static non-motor and steps along the other, the effect of stochastic binding of its non-motor end to either microtubule results in a net force of zero (e.g. the two motors on the right-hand side of the cross-linked microtubules have equal and opposite effects on microtubule sliding, producing no net sliding or force). However, a higher motor binding affinity to microtubule minus ends would allow for sliding and end alignment (for an excellent treatment of these mechanisms please see [17]).