Organization and dynamics of the spindle − Rakyat Biologi

In the spindle, minus ends of microtubules are embedded and stabilized at centrosomes or at other microtubules (see 1.1.2.1. and 1.1.2.3.). Depending on the position of the plus ends, microtubules are classified into three populations: astral, kinetochore and polar microtubules (Fig.2.). Astral microtubules radiate from centrosomes towards the cell cortex and position the spindle within the cell (Grill et al., 2003). The kinetochore microtubules are microtubules that attach kinetochores with their plus ends. The main role of kinetochore microtubules is to pull chromosomes at their kinetochores towards spindle poles. Several microtubules attached to a single kinetochore form a bundle, called the kinetochore fibre (McDonald et al., 1992). The third type, the polar microtubules are microtubules which emanate from the opposite poles and interweave with each other at the spindle equator and/or interact with chromosome arms (Mastronarde et al., 1993). Studies in mammalian cells showed that interaction between microtubules of opposite polarity at the spindle equator, the antiparallel microtubule bundles, is favoured over interaction between microtubules of the same polarity, the parallel microtubule bundles.

Interaction between microtubules is mediated by MAPs belonging to motor and non-motor proteins and is important for establishment of the bipolar structure of the spindle (Sharp et al., 2000). Motor proteins use energy from ATP hydrolysis to move along microtubules (Vale and Fletterick, 1997; Oiwa and Sakakibara, 2005). There are two classes of motors: kinesins and dyneins. Most kinesins move towards the plus end of microtubules (plus end directed motors), while dyneins move towards the minus ends (minus end directed motors). Motors moving along one microtubule can interact with another microtubule and slide the microtubules relative to each other (Sharp et al., 2000). Eg5/Klp61F preferentially crosslinks antiparallel microtubules and slides them apart promoting centrosome separation in prometaphase (Fig.2.; see 1.2.2.; Sawin et al., 1992; Sharp et al., 1999; Sharp et al., 2000; van den Wildenberg et al., 2008). This microtubule motion, generated by Eg5/Klp61F also contributes to microtubule flux (see below and 1.2.2.; Miyamoto et al., 2004; Brust-Mascher Scholey 2002). Some motors move along microtubule and simultaneously bind another microtubule of the same polarity as a cargo. Such activity is attributed to dynein and Ncd and has been shown to have an important role in spindle pole focusing (see 1.2.2.; Goshima et al., 2005). Non-motor proteins, such as NuMa, TACC, Msps also have been shown to promote spindle pole focusing (Merdes et al., 1996; Lee et al., 2001). Much about the role of MAPs in the spindle architecture has been revealed in studies in systems without centrosomes (see 1.2.2.).

Despite the stable architecture, the spindle is a very dynamic structure. While plus ends of kinetochore microtubules constantly polymerize, the minus ends at the poles de-polymerize (Mitchison, 1989). Together with sliding of antiparallel microtubules, this results in a continuous movement of tubulin towards the spindle poles, called the poleward flux (Mitchison, 1989).