Editors' ChoiceMitosis

Small GTPase Controls Chromosome Segregation

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Science's STKE  21 Sep 2004:
Vol. 2004, Issue 251, pp. tw337
DOI: 10.1126/stke.2512004tw337

About 150 members comprise the human small guanosine triphosphatase (GTPase) protein superfamily, with diverse cellular functions ranging from regulation of the cytoskeleton and migration to cell proliferation and nuclear transport. By searching the human genome database, screening a human brain cDNA library, and conducting phylogenetic analysis, Okai et al. have discovered yet more family members that fall into an atypical subset of GTPases. Named Gie1 and Gie2 (GTPases indispensible for equal segregation of chromosomes), the new members share about 30% amino acid identity with other small GTPases. Although they contain the highly conserved GTP-binding and effector domains, the proteins lack lipid-modification motifs, classifying them into a distinct subfamily. Homologs were identified in Drosophila, mouse, rat, and worm, although not in yeast, which indicates conservation in multicellular organisms. Gie mRNAs were detected in various human tissues, and the proteins were detected in both GTP- and GDP-bound states, indicating that the proteins cycle between active and inactive forms. Expression of a dominant-negative form of Gie1 in a cultured human cell line caused the appearance of micronuclei and abnormal chromosome segregation. Knockdown of Gie in Drosophila cells also blocked normal sister chromosome segregation but did not block the progression of mitosis. Gie colocalized with microtubules in the cytoplasm during interphase but redistributed to the mid-zone of the mitotic spindle during anaphase and to the mid-body in late telophase. Gie protein also immunoprecipitated with α and β tubulin, independent of its nucleotide-binding state. The authors suggest that Gie proteins use the mitotic network for localization during mitosis. Its effectors, which remain to be identified, may localize to the spindle mid-zone and mid-body to control chromosome segregation.

T. Okai, Y. Araki, M. Tada, T. Tateno, K. Kontani, T. Katada, Novel small GTPase subfamily capable of associating with tubulin is required for chromosome segregation. J. Cell Sci. 117, 4705-4715 (2004). [Abstract] [Full Text]

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