Figure 4.
Kinetochore tension as a crucial centrosome clustering mechanism. (A) Model of kinetochore-facilitated clustering: (1) Outwardly-directed, dynein-mediated tension, Fd (direction indicated by purple arrows), is partly offset by inwardly-directed, kinetochore-mediated tension, Fk (direction indicated by cyan arrows). (2) The sum of the forces, Fnet (direction indicated by magenta arrows), is directed to one or the other pole. (3) As a result, centrosomes are brought closer together, although kinetochore-mediated tension alone is probably insufficient to overcome outwardly-directed forces. (4) HSET between antiparallel microtubules provides further inwardly-directed tension, permitting tight clustering. (b) Model of declustering without kinetochore-generated tension: (1) Without tension at the kinetochore, dynein is unopposed. (2) As a result, centrosomes are pulled toward the cortex, and (a) if HSET is present, some pole-focusing occurs, although this is insufficient to cause centrosomes to coalesce; however, (b) without HSET, complete declustering results. (c). Induction of robust declustering results in multipolar spindle formation and cell death. On the left, a human prostate cancer PC3 cell exhibits severely high-grade multipolarity. On the right, a multipolar cell of the same line succumbs to mitotic catastrophe. (microtubules=red; DNA=blue)