The GTPase RAN regulates multiple steps of the centrosome life cycle

Growing lines of evidence implicate the small GTPase RAN, its regulators and effectors-predominantly, nuclear transport receptors-in practically all aspects of centrosome biology in mammalian cells. These include duplication licensing, cohesion, positioning, and microtubule-nucleation capacity. RAN cooperates with the protein nuclear export vector exportin 1/CRM1 to recruit scaffolding proteins containing nuclear export sequences that play roles in the structural organization of centrosomes. Together, they also limit centrosome reduplication by regulating the localization of key "licensing" proteins during the centrosome duplication cycle. In parallel, RAN also regulates the capacity of centrosomes to nucleate and organize functional microtubules, and this predominanlty involves importin vectors: many factors regulating microtubule nucleation or function harbor nuclear localization sequences that interact with importin molecules and such interaction inhibits their activity. Active RANGTP binding to importin molecules removes the inhibition and releases microtubule regulatory factors in the free productive form. A dynamic scenario emerges, in which RAN is pivotal in linking spatiotemporal control of centrosome regulators to the cell cycle machinery.