Interplay Between Spindle Architecture and Function - International Review of Cell and Molecular Biology - page 83

cellular environment. In this review, we discuss the phenomenology and underlying
mechanisms that describe how spindle architecture is optimized to promote robust
chromosome segregation in diverse cell types. We focus on the role of MT dynamics,
stabilization, and transport in an effort to understand how the molecular mechanisms
governing these processes lead to the formation of the functional, steady-state spindle
structure. Finally, we investigate the basis of spindle variation and discuss why spindles
take on certain forms in different cell types. The recent advances in understanding spin-
dle biology have shown that spindle assembly utilizes multiple but common pathways
weighted differently in different cells and organisms. These assembly differences are
correlated with variations in spindle architectures that may influence the regulation
of molecules in the spindle. Overall, as architectural features of different spindles are
elucidated, the available comparative genomic data should provide structural and
mechanistic insight into how a spindle is built, how dynamic interactions lead to a
steady-state structure, and how spindle function is disrupted in disease.
1. INTRODUCTION
The generation and continuation of life depends on cell division
through gametogenesis, development, and homeostatic maintenance of tis-
sues and organisms. Accurate chromosome segregation is essential for
genome stability, and deviations in the process can generate chromosomal
changes associated with evolution or cause cellular transformation and
cancer ( Chen et al., 2012; Gordon et al., 2012; Holland and Cleveland,
2012 ). To achieve high fidelity genome transmission, a dynamic architec-
tural arrangement of the microtubule (MT) cytoskeleton called the spindle
is assembled at the onset of mitosis or meiosis. The spindle provides the scaf-
fold and mechanism for force generation to physically separate chromo-
somes to daughter cells, and also determines the position of the
cytokinetic furrow ( Glotzer, 2003 ). Across eukaryotic biology, cell size
and shape vary dramatically, requiring complex spatial information to be
integrated by the spindle, which may adjust by altering spindle factors
and their organization. Genomewide screening and proteomic studies have
provided comprehensive lists of spindle-associated proteins and there is evi-
dence that nonprotein components other than chromosomes such as RNA
also function as integral spindle components ( Blower et al., 2005; Bonner
et al., 2011; Chang et al., 2004; Gache et al., 2010; Goshima et al., 2007;
Groen et al., 2011 ). Together with functional investigation of individual fac-
tors, these studies provide a critical foundation for investigating the physi-
ological mechanisms that tune spindle size, morphology, and function.