title: The GTPase Gem and its partner Kif9 are required for chromosome alignment, spindle length control, and mitotic progression.
abstract: Within the Ras superfamily, Gem is a small GTP-binding protein that plays a role in regulating Ca(2+) channels and cytoskeletal remodeling in interphase cells. Here, we report for the first time that Gem is a spindle-associated protein and is required for proper mitotic progression. Functionally, loss of Gem leads to misaligned chromosomes and prometaphase delay. On the basis of different experimental approaches, we demonstrate that loss of Gem by RNA interference induces spindle elongation, while its enforced expression results in spindle shortening. The spindle length phenotype is generated through deregulation of spindle dynamics on Gem depletion and requires the expression of its downstream effector, the kinesin Kif9. Loss of Kif9 induces spindle abnormalities similar to those observed when Gem expression is repressed by siRNA. We further identify Kif9 as a new regulator of spindle dynamics. Kif9 depletion increases the steady-state levels of spindle α-tubulin by increasing the rate of microtubule polymerization. Overall, this study demonstrates a novel mechanism by which Gem contributes to the mitotic progression by maintaining correct spindle length through the kinesin Kif9.
authors.affiliation: Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération, Centre National de la Recherche Scientifique–Unité Mixte de Recherche (CNRS-UMR) 5088, Toulouse, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Andrieu
authors.forename: Muriel
authors.initials: M
authors.lastname: Quaranta
authors.forename: Corinne
authors.initials: C
authors.lastname: Leprince
authors.forename: Anastassia
authors.initials: A
authors.lastname: Hatzoglou
mesh_terms: D002460:Cell Line; D020090:Chromosome Segregation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D008941:Spindle Apparatus / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: C435207:KIF9 protein, human; D008565:Membrane Proteins; D014404:Tubulin; D049452:Green Fluorescent Proteins; D016547:Kinesins; C490245:GEM protein, human; D020559:Monomeric GTP-Binding Proteins