Interplay Between Spindle Architecture and Function - International Review of Cell and Molecular Biology - page 100

seen upon Augmin depletion in Drosphila were defects in the establishment
of the anaphase MT arrays, suggesting that branching MT nucleation is most
important when antiparallel arrays of MTs are prominent ( Uehara et al.,
2009 ). Consistent with this idea, Augmin was found to be dispensable for
bipolar spindle formation in human cells whose spindles normally form in
a centrosome-driven pathway, and the presence of centrosomes in Xenopus
spindles largely mitigated the effects of Augmin depletion ( Petry et al.,
2011 ). Together, these data imply that unique spindle architectures are likely
established through different modes of MT nucleation and organization,
although we do not yet understand how branching MT nucleation sites
are positioned and regulated.
4. MOLECULAR MECHANISMS DEFINING SPINDLE
ARCHITECTURE: MICROTUBULE STABILITY
AND TRANSPORT
The metaphase spindle maintains its steady-state morphology for
minutes to hours through the dynamic activities of a hundred or more pro-
teins. To understand how common features of spindle architecture arise and
points at which the basic spindle structure can be elaborated, a complete
understanding of the individual reactions within the spindle must be
achieved. This effort, of course, has yet to be realized, but we will next sum-
marize known mechanisms necessary for robust spindle assembly with a
focus on MT organization. We will examine the details of some
MT-stabilizing, -destabilizing, and -transporting proteins. Most spindle pro-
teins fit into one of these categories, some fit into more than one, while some
have activities that are poorly understood. We focus on examples from a
structure function perspective, describing how specific proteins and activ-
ities contribute to spindle assembly and architecture.
4.1. Microtubule-stabilizing proteins
As described earlier, several pathways of MT nucleation during spindle for-
mation have been characterized. However, the precise mechanism(s) by
which MTs nucleate at sites other than the centrosome remains unclear,
specifically whether or not all modes require g -TuRC, or if other factors
such as TPX2 or Augmin are capable of nucleating MTs independently.
At the biochemical level, it is extremely difficult to distinguish between
stabilization of very small tubulin assemblies and true nucleation, although
the need to delineate between alternate mechanisms may not be crucial if