20 - Roles of Cytoplasmic Dynein During Mitosis

Abstract

Cytoplasmic dynein is an abundant microtubule motor protein implicated widely in intracellular transport. Investigations into mitotic dynein activity have intensified recently with the development of new model systems, the identification of dynein binding partners, and the use of genetic and siRNA screens. This chapter summarizes what is known about the role of cytoplasmic dynein during mitosis and proposes novel models for functional complexity. Several vertebrate model systems have paved the way for progress in dissecting mitotic dynein. For imaging of mitotic dynein, cultured cell lines have been a workhorse system. Cultured cells provide the advantages of simplified imaging, synchronization, transfection of plasmid constructs, and siRNA/shRNA. During mitosis, the significance of the spindle pole localization for dynein is complicated by the overlapping roles dynein plays as a motile complex transporting MTOC components and a more static complex crosslinking microtubules. During progression through mitosis, the next population of dynein that is considered functions at the cell cortex. The primary functions for cortical dynein are to interact with astral microtubules and to position the spindle. In metazoans, dynein is detected at kinetochores only after nuclear envelope breakdown and it is proposed to play a direct role in nuclear envelope breakdown itself. Furthermore, mitotic phosphorylation of dynein has been detected across multiple model systems. A few questions that remain in this understanding are the functions of site-specific accessory proteins and the role of dynein complexity in site-specific ageing.