Novel small GTPase subfamily capable of associating with tubulin is required for chromosome segregation.
The small GTPase superfamily, which includes the Ras, Rho/Rac, Rab, Arf and Ran subfamilies, serves as a signal transducer to regulate cell proliferation and differentiation, actin cytoskeleton, membrane trafficking, and nuclear transport. Here, we identify novel GTPases (human Gie1 and Gie2) that form a distinct subfamily of the small GTPases in terms of their sequences and intracellular function. Gie stands for 'novel GTPase indispensable for equal segregation of chromosomes', and this subfamily is conserved in multicellular organisms. Expression of dominant-negative Gie mutants in mammalian cells or knockdown of Gie transcripts using RNA interference in Drosophila S2 cells induced abnormal morphology in the chromosome segregation. Gie protein has ability to bind to tubulin and localizes with microtubules on the spindle mid-zone in late mitosis. Furthermore, overexpression of Gie mutants that lack putative effector domains but have tubulin-binding ability induced micronucleus formation. Thus, this is the first report showing that a small GTPase subfamily capable of associating with microtubules might be involved in chromosome segregation.
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Takuro
T
Okai
Yasuhiro
Y
Araki
Minoru
M
Tada
Toshiyuki
T
Tateno
Kenji
K
Kontani
Toshiaki
T
Katada
D020727:ADP-Ribosylation Factors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002869:Chromosome Aberrations; D020090:Chromosome Segregation; D004331:Drosophila melanogaster; D020558:GTP Phosphohydrolases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D020033:Protein Isoforms / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016415:Sequence Alignment; D014018:Tissue Distribution; D014404:Tubulin / Q000378:metabolism*
C511801:ARL8B protein, human; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D014404:Tubulin; C512609:ARL8A protein, human; D020558:GTP Phosphohydrolases; D020727:ADP-Ribosylation Factors