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GTPases regulate mitotic cell logistics

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Traffic of vesicles among intracellular compartments controls a large variety of cell functions including cell division. Recent findings showing that several trafficking molecules, which regulate vesicles biogenesis and transport in interphase, also localize to the mitotic apparatus (spindle microtubules, ...

Traffic of vesicles among intracellular compartments controls a large variety of cell functions including cell division. Recent findings showing that several trafficking molecules, which regulate vesicles biogenesis and transport in interphase, also localize to the mitotic apparatus (spindle microtubules, centrosomes or kinetochores), and interact with key mitotic players, have fueled investigations of a crosstalk between membrane trafficking and mitosis.

Mitosis, which starts with nuclear envelope breakdown (NEB), has long been regarded as a “membrane free” process in higher eukaryotes. In fact, however, nuclear envelope components, traditionally believed to be "stored" in the endoplasmic reticulum until nuclear envelope reformation at mitotic exit, come to a "second life" after NEB: lamin, many nucleoporins and signal-mediated transport receptors relocate to the mitotic apparatus and direct multiple pathways of spindle organization in processes orchestrated by the GTPase RAN. New functions of nuclear transport components are emerging, in mitotic spindle dynamics and positioning. Mitosis-specific SUMO conjugation of factors regulating the mitotic apparatus, and/or its interaction with kinetochores, represents a new arena of RAN control. The modes of this control are incompletely understood and how RAN signals propagate in cells with very different topological features is still being intensely investigated. Interestingly, organisms that segregate chromosomes in a "closed" mitosis have been shown to experience a mitosis-specific nuclear translocation of the GTP hydrolysis-activating factor for RAN, RANGAP1, which is proposed to remodel RAN signals in coincidence with virtual NEB.

Similarly to nuclear envelope components, membrane trafficking molecules also play specific mitotic functions. While early investigations of the role of vesicles in cell division focussed on cytokinesis, a step requiring indeed vesicle-mediated transport of molecules and membranes at the site of cell abscission, more recent studies also implicate small GTPases of the Rab family in mitotic progression. Some Rab family GTPases were recently shown to localize on vesicles that move within the spindle, revealing that a specialized vesicle-mediated transport mechanism occurs during mitosis, an unexpected and previously unrecognized process. Importantly, this has been proven to control proper spindle assembly. The composition of these vesicles, their origin and the possible release of cargo to non-membranous mitotic structures, e.g. at centrosomes, are some of the many open questions.

Studies of the mitotic roles of membrane trafficking and transport molecules bridge investigations across several disciplines, from classical genetics to biochemistry, cell biology, biophysics and modelling, for which cross-talking might be difficult. Here we aim to bring in contact research groups using different approaches and model system. By sharing opinions, data and reviewing what has been found so far, we wish to set an open discussion with scientists interested in this emerging field.


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