A main player in the latter pathway is a GTPase Ran, whose activator, RCC1, is concentrated on the chromosomes. Thereby, Ran locally activates several downstream proteins required for spindle assembly, such as the microtubulestabilising protein HURP and the crosslinker kinesin-14. TPX2 is one of the best-characterised targets of Ran. This conserved microtubule-associated protein was originally identified as a protein required for targeting kinesin-12 to the spindle pole in Xenopus egg extracts. Subsequent functional studies have established that TPX2 is essential for spindle assembly, in particular for spindle pole organisation in a variety of cell types. TPX2 is imported into the nucleus by importin binding during interphase and is subsequently activated by the removal of importin by RanGTP following nuclear envelope breakdown . Several conserved domains have been identified in TPX2, including regions responsible for nuclear localisation, activation of the Aurora A kinase, microtubule nucleation and stabilisation, and kinesin-5 binding. The mechanism of Aurora A activation has been elucidated at the atomic level, and structure-function studies have clarified the importance of this domain in spindle size control and suggested its role in spindle assembly itself . Although the microtubule nucleation activity has been shown in vitro, the physiological significance of this activity has been controversial; lack of microtubule generation in the absence of TPX2 in cells has been suggested to be due to stabilisation defects rather than nucleation problems. TPX2 is most concentrated at spindle poles partly due to motor-dependent transport, but it is also localised all along the spindle microtubules. Although the organisation of these domains is generally conserved among multicellular organisms, there are 2 exceptions. In Caenorhabditis elegans, the TPX2-like protein appears to be missing all the conserved domains other than that responsible for Aurora A activation. Another, perhaps more mysterious issue is that homologous proteins to TPX2 have not been found in the genome of Drosophila melanogaster, one of the most popularly used model animal species for cell division research, although HURP and kinesin-14, 2 other Ran targets have been identified as the nuclear and spindle proteins. The Drosophila Ssp1/Mei-38 gene was identified in 2 independent studies. In a genome-wide RNAi screen for spindle morphology, knockdown of this gene elevated the percentage of spindles with slightly abnormal morphology, such as shorter, monastral bipolar or monopolar spindles. On the other hand, genetic screening by Baker and Carpenter identified an allele of mei-38 for elevated levels of X chromosome nondisjunction in female flies, and GDC-0879 recent cloning by Wu et al. revealed that Mei-38 is identical to Ssp1. The null mutant exhibits defects in meiotic spindle morphology in female flies. However, although slight spindle organization defects are seen in mitotic cells in the larval brain, the mutant is completely viable with no noticeable defects.