Tiam1-Rac signaling counteracts Eg5 during bipolar spindle assembly to facilitate chromosome congression.

ABSTRACT: Centrosome separation, critical for bipolar spindle formation and subsequent chromosome segregation during mitosis, occurs via distinct prophase and prometaphase pathways. Kinesin-5 (Eg5), a microtubule (MT) motor, pushes centrosomes apart during bipolar spindle assembly; its suppression results in monopolar spindles and mitotic arrest. Forces that antagonize Eg5 in prophase are unknown. Here we identify a new force generating mechanism mediated by the guanine nucleotide exchange factor (GEF) Tiam1, dependent on its ability to activate the GTPase Rac. We reveal that Tiam1 and Rac localize to centrosomes during prophase and prometaphase, and Tiam1, acting through Rac, ordinarily retards centrosome separation. Importantly, both Tiam1-depleted cells in culture and Rac1-deficient epithelial ce

SUBMITTER: Woodcock SA 

PROVIDER: S-EPMC2989435 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature