Figure 17–27 Activation of the GTPase Ran around mitotic chromosomes. The Ran protein, like other members of the small gTpase family (discussed in Chapter 15), can exist in two conformations depending on whether it is bound to gdp (inactive state) or gTp (active state). The localization of active Ran in mitosis was determined using a protein that emits fluorescence at a specific wavelength when it is activated by Ran-gTp. In the metaphase human cell shown here, Ran activity (yellow and red) is highest around the chromosomes, between the poles of the mitotic spindle (indicated by asterisks). (From p. kaláb  et al., Nature 440:697–701, 2006. With permission from macmillan publishers Ltd.) nucleation antiparallel cross-linking outward push focusing of poles by by kinesin-5 by kinesin-4,10 dynein and kinesin-14 – – –
Figure 17–28 Spindle self-organization by motor proteins. mitotic chromosomes stimulate the local activation of proteins that nucleate and promote the formation of microtubules in the vicinity of the chromosomes. kinesin-5 motor proteins (see Figure 17–25) organize these microtubules into antiparallel bundles, while plus-end directed kinesins-4 and 10 link the microtubules to chromosome arms and push minus ends away from the chromosomes. dynein and kinesin-14 motors, together with numerous other proteins, focus these minus ends into a pair of spindle poles.
The ability of chromosomes to stabilize and organize microtubules enables cells to form bipolar spindles in the absence of centrosomes. Acentrosomal spindle assembly is thought to begin with the formation of microtubules around the chromosomes. Various motor proteins then organize the microtubules into a bipolar spindle, as illustrated in Figure 17–28.
Cells that normally lack centrosomes, such as those of higher plants and many animal oocytes, use this chromosome-based self-organization process to form spindles. It is also the process used to assemble spindles in certain animal embryos that have been induced to develop from eggs without fertilization (that is, parthenogenetically); as the sperm normally provides the centrosome when it fertilizes an egg, the mitotic spindles in these parthenogenetic embryos develop without centrosomes (Figure 17–29). Even in cells that normally contain centrosomes, the chromosomes help organize the spindle microtubules and, with the help of various motor proteins, can promote the assembly of a bipolar mitotic spindle if the centrosomes are removed. Although the resulting acentrosomal spindle can segregate chromosomes normally, it lacks astral microtubules, which are responsible for positioning the spindle in animal cells; as a result, the spindle is often mispositioned in the cell.
kinetochores attach sister Chromatids to the spindle