Rod-Zw10-Zwilch: a key player in the spindle checkpoint.

The spindle checkpoint assures the proper segregation of chromosomes during mitosis. The best-characterized components of the checkpoint were originally identified in budding yeast. But three proteins with no yeast homologs--Rod, Zw10 and Zwilch--also play a crucial, but poorly understood, role in the metazoan spindle checkpoint. Recent work has begun to reveal the function of these proteins. The three form a complex (the RZZ complex), which is required for the recruitment of two better-known components of the kinetochore--the dynein-dynactin complex, and Mad1-Mad2. It has now been established that RZZ is directly or indirectly responsible for both Mad1-Mad2 recruitment to unattached kinetochores and its subsequent shedding from kinetochores following MT attachment, and thus is involved in both the activation and inactivation of the checkpoint. This review (which is part of the Chromosome Segregation and Aneuploidy series) covers recent developments in our understanding of RZZ dynamics and its function in the checkpoint.