Interplay Between Spindle Architecture and Function - International Review of Cell and Molecular Biology - page 99

A B

Microtubule amplification Kinetochore-fiber stabilization

Augmin g -TuRC

TPX2

MCRS1
-

- + HURP

Kinesin-13

F

Pole focusing

C

Microtubule stabilization

NuMA crosslinking

+

Dynein XMAP215

-

- +

-

-

+

+ Patronin

E

Microtubule sliding

D

Microtubule destabilization

Kinesin-13

-

+

Kinesin-5

-

+ -

-

-

Katanin

-

-

- +

-

+

Figure 3.5 Mechanisms of spindle-associated proteins and organization of the spindle.
(A) The Augmin complex stimulates amplification of MTs through branched nucleation
in the same polarity as existing MTs, enhancing the formation kinetics and density of the
overlapping tiled array of spindle MTs. (B) Kinetochore fibers are formed by the action of
bundling proteins, such as HURP and TPX2, and are provided additional stability by pro-
teins that protect the minus-ends, such as MCRS1, from depolymerization by kinesin-13
motors. (C) Microtubule stabilization in the spindle structure is affected by many differ-
ent functional mechanisms, such as promoting polymerization (XMAP215) or by protec-
tion from destabilization (Patronin). (D) Microtubule destabilization, on both spindle
MTs and kinetochore fibers, can occur through severing by enzymes such as Katanin
or by end-depolymerization via kinesin-13s. Destabilizing proteins have specific and
varied locations throughout the spindle, suggesting the importance of local
destabilizing activity in the spindle. (E) In the antiparallel overlap zone, the tetrameric
kinesin-5 motor walks to the plus-ends of neighboring MTs, effectively sliding the
minus-ends poleward. (F) Pole focusing occurs through the concerted effort of
minus-end directed motors, such as dynein, which carry MTs as cargo toward minus-
ends. Additionally, cross-linking activity by NuMA is directed to the poles by dynein
transport, where large oligomers create a MT clustering force.

likely produce a structure akin to a tiled array, held together by cross-linking
factors and molecular motors. In Xenopus egg extract containing spindles
with tiled-array architecture self-organized around chromatin-beads, Aug-
min depletion defects were severe and resulted in abnormally long, multi-
polar spindles ( Petry et al., 2011 ). In contrast, the major mitotic phenotype