Cooperative mechanisms of mitotic spindle formation.

Cooperativity is well known to promote the speed of some biochemical reactions by accelerating the activity of enzymes. Recent studies have shown that cooperative interactions also function during the formation of a complex cellular structure, the mitotic spindle. Capture of kinetochores by dynamic astral microtubules was originally proposed as the basis of spindle formation. However, mounting evidence indicates that a more complex series of events occurs. It is now clear that there are multiple microtubule nucleation and capture sites throughout the spindle. Kinetochores, centrosomes and microtubules play multiple roles in establishing connections between spindle components and integrating them into a common structure. These data support a modified search-and-capture model that incorporates additional assembly pathways coordinated by a RanGTP gradient.