2) Initial kinetochore-microtubule interaction

Kinetochores are large protein complexes formed on chromosome regions known as centromeres. For high-fidelity chromosome segregation, kinetochores must be properly captured on the mitotic spindle before anaphase onset (Refs. 2, 5). Kinetochores initially attach to the lateral surface of a single microtubule extending from a spindle pole (Refs. 3, 6); this process is often facilitated by microtubules generated at kinetochores (Figure, step 1: Ref. 1). Once kinetochores are loaded onto a spindle-pole microtubule, they are transported poleward by the microtubule (step 2; Refs. 3, 4, 6). We have developed a novel assay to visualize these steps in live cells, and have identified crucial regulatory factors. We are studying further how this process is regulated.

Figure. The figure depicts kinetochore-microtubule interactions during prometaphase (steps 1-3), metaphase (step 4) and anaphase (step 5). Kinetochores initially interact with the surface of a microtubule, move towards a spindle pole and bi-orient on the spindle before the onset of anaphase. See details in Refs 2, 5.

< References >

1. Kitamura E, Tanaka K, Komoto S, Kitamura Y, Antony C & Tanaka TU. Kinetochores generate microtubules with distal plus ends: their roles and limited lifetime in mitosis. Dev Cell, 18, 248-59. (2010).

2. Tanaka TU & Desai A. Kinetochore-microtubule interactions: the means to the end. Curr Opin Cell Biol, 20, 53-63. (2008)

3. Kitamura E, Tanaka K, Kitamura Y & Tanaka TU. Kinetochore-microtubule interaction during S phase in Saccharomyces cerevisiae. Genes Dev, 21, 3319-30. (2007).

4. Tanaka K, Kitamura E, Kitamura Y & Tanaka TU.  Molecular mechanisms of microtubule-dependent kinetochore transport towards spindle poles. J Cell Biol, 178, 269-81. (2007).

5. Tanaka TU, Stark MJR & Tanaka K. Kinetochore capture and bi-orientation on the mitotic spindle. Nat Rev Mol Cell Biol, 6, 929-42. (2005)

6. Tanaka K, Mukae N, Dewar H, van Breugel M, James EK, Prescott AR, Antony C & Tanaka TU.  Molecular mechanisms of kinetochore capture by spindle microtubules. Nature 434, 987-94. (2005).