Interplay Between Spindle Architecture and Function - International Review of Cell and Molecular Biology - page 94

A B C

Centrosome search-and-capture Chromatin-mediated Kinetochore-mediated

?

RanGTP

TPX2

Importin Importin α α / / β β

?

g -TuRC

Augmin

Figure 3.4 Spindle assembly pathways and mechanisms of MT nucleation. (A)
Centrosome-mediated search-and-capture proceeds by nucleation of MTs from the
g-tubulin ring complex embedded in the centrosome. Orientation of chromosomes
in a toroidal arrangement around the center of the nascent spindle, with exposed kinet-
ochores, facilitates connections between these centrosomal MTs and kinetochores. (B)
The chromatin-mediated self-assembly pathway is governed by a spatial gradient of
RanGTP, which stimulates the release of MAPs in the vicinity of the chromosomes.
One confirmed cargo, TPX2, has a role in nucleation of MTs in this pathway, but the
mechanism is unknown. The Augmin complex, which recruits g-TuRC, amplifies MTs
nucleated around the chromosomes in this pathway. (C) MTs have been shown to nucle-
ate directly from kinetochores; however, the mechanism is not yet elucidated but might
share some commonalities with the chromatin-mediated pathway.

interactions between MTs and kinetochores. Orienting kinetochores in this
way predisposes them for MT interactions, facilitating the formation of
end-on MT attachments and biorientation, both in vivo and in silico
( Magidson et al., 2011 ).
Despite the prevalence of centrosomes, the existence of meiotic or plant
spindles that lack them, together with studies employing centrosome abla-
tion, clearly demonstrate that they are not essential for bipolar spindle assem-
bly ( Khodjakov et al., 2000 ). However, if the centrosome was removed
by microsurgery early in the cell cycle, a MTOC-lacking centriole was