Chapter Three - Interplay Between Spindle Architecture and Function

Abstract

The mitotic spindle performs the universal and crucial function of segregating chromosomes to daughter cells, and all spindles share common characteristics that facilitate this task. The spindle is built from microtubule (MT) polymers and hundreds of associated factors that assemble into a dynamic steady-state structure that is tuned to the 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 spindle 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.