Dynein at the kinetochore: Timing, Interactions and Functions

Abstract

Kinetochores have been proposed to play multiple roles in mitotic chromosome alignment, including initial microtubule (MT) capture, monitoring MT attachments, prometaphase and anaphase chromosome movement and tension generation at metaphase. In addition, kinetochores are essential components of the spindle assembly checkpoint (SAC), and couple chromosome alignment with SAC silencing at metaphase. Although the molecular details of these activities remain under investigation, cytoplasmic dynein has been implicated in several aspects of MT and SAC regulation. Recent work clarifies the contribution of dynein to MT interactions and to events that drive anaphase onset. This review summarizes these studies and provides new models for dynein function.

Figure 1

Changes in Kinetochore Dynein During Mitosis. Dynein is initially recruited to kinetochores before MT attachment (A.) and remains at kinetochores during the process of mono-orientation and association with the spindle (B.) After bi-oriented MT attachments are achieved (C.), dynein undergoes poleward movement and labels K-fibers and spindle poles. By anaphase onset (D.), dynein is prominent on spindle fibers but undetectable at kinetochores.

Figure 2

Model 1: Multiple Populations of Dynein Coexist at Kinetochores. One possibility suggested by the literature is that multiple populations of dynein coexist, are recruited by distinct receptors and perform different functions. This would allow dynein to mediate diverse functions such as MT attachment, generation of tension and SAC silencing. Receptors for these dynein subsets include RZZ, LIS-1/nudE/EL/nudC/CL, dynactin and Spindly.

Figure 3

Model 2: Sequential Interaction Model. A second possibility consistent with the literature is that dynein undergoes changes in binding that are coupled to MT attachment, kinetochore stretch and chromosome alignment. Initially recruited through a direct interaction between phosphorylated dynein and zw10 (t=1), dynein is dephosphorylated (t=2), shifts binding from zw10 to dynactin (t=3), and translocates away from kinetochores (t=4). In this model, some binding partners are responsible for transferring dynein from zw10 to dynactin, whereas others are responsible for activating dynein as a motor.