Interplay Between Spindle Architecture and Function - International Review of Cell and Molecular Biology - page 84

The catastrophic potential of chromosome segregation errors provides a
strong selective pressure to form a functionally robust spindle. The specific
characteristics of a given cell type, including its size, shape, and contents, will
drive diversification of the spindle to suit the particular needs of the cell. In
this review, we first describe the architectural features common to all spin-
dles and the fundamental mechanisms of MT dynamics and organization.
We then expand upon the key activities that generate spindle architecture,
including MT nucleation, transport, and stability within the spindle.
Elaborations on the basic spindle theme are then discussed. Throughout,
we utilize specific examples to illustrate general principles of spindle biology
and describe the experimental and computational results that are generating
a clearer picture of spindle assembly, architecture, and function.
2. CONSERVED FEATURES OF THE METAPHASE SPINDLE
Chromosome segregation, the common function of all spindles, is
preceded by the formation of a steady-state structure at metaphase in which
duplicated chromosomes are attached to spindle MTs and poised to separate
to opposite ends of the cell at anaphase. While the details of spindle assembly
and architecture vary across species and cell types, universal principles oper-
ate to ensure chromosome segregation.
2.1. Microtubules and their dynamics
The fundamental structural unit of the spindle is the MT ( Fig. 3.1 ), whose
dynamics and organization are modulated by hundreds of MT-associated
proteins (MAPs) and motors. MTs are polymers made of a - and b -tubulin
heterodimers that bind head-to-tail to form polarized protofilaments, and, in
turn, 13 protofilaments associate laterally and in the same orientation to
form a hollow rigid tube about 25 nm in diameter ( Chretien et al., 1992;
Downing and Nogales, 1998 ). The asymmetry of the tubulin dimer confers
polarity to the polymer—the end with exposed a -tubulin is called the
minus-end, while the b -tubulin end is called the plus-end—leading to dif-
ferent polymerization and depolymerization reactions at each end.
MTs may be growing or shrinking and can abruptly switch between the
two states, a behavior termed dynamic instability ( Mitchison and Kirschner,
1984a,b ). Following polymerization, hydrolysis of GTP bound to b -tubulin
occurs rapidly within the lattice of the MT, and MTs possessing a terminal
“cap” of tubulin dimers that have not yet hydrolyzed their GTP can