Chromosome segregation requires the formation of K-fibres, microtubule bundles that attach sister kinetochores to spindle poles. Most K-fibre microtubules originate around the chromosomes through a non-centrosomal RanGTP-dependent pathway and become oriented with the plus ends attached to the kinetochore and the minus ends focused at the spindle poles. The capture and stabilization of microtubule plus ends at the kinetochore has been extensively studied but very little is known on how their minus-end dynamics are controlled. Here we show that MCRS1 is a RanGTP-regulated factor essential for non-centrosomal microtubule assembly. MCRS1 localizes to the minus ends of chromosomal microtubules and K-fibres, where it protects them from depolymerization. Our data reveal the existence of a mechanism that stabilizes the minus ends of chromosomal microtubules and K-fibres, and is essential for the assembly of a functional bipolar spindle.
SummaryThe mitotic spindle is structurally and functionally defined by its main component, the microtubules (MTs). The MTs making up the spindle have various functions, organization and dynamics: astral MTs emanate from the centrosome and reach the cell cortex, and thus have a major role in spindle positioning; interpolar MTs are the main constituent of the spindle and are key for the establishment of spindle bipolarity, chromosome congression and central spindle assembly; and kinetochore-fibers are MT bundles that connect the kinetochores with the spindle poles and segregate the sister chromatids during anaphase. The duplicated centrosomes were long thought to be the origin of all of these MTs. However, in the last decade, a number of studies have contributed to the identification of noncentrosomal pathways that drive MT assembly in dividing cells. These pathways are now known to be essential for successful spindle assembly and to participate in various processes such as K-fiber formation and central spindle assembly. In this Commentary, we review the recent advances in the field and discuss how different MT assembly pathways might cooperate to successfully form the mitotic spindle.
The XRHAMM-γTuRC complex is the target for activation by RanGTP that promotes an interaction between TPX2 and XRHAMM. The resulting TPX2-RHAMM-γTuRC supracomplex fulfills the two essential requirements for the activation of MT nucleation by RanGTP: NEDD1 phosphorylation on S405 by the TPX2-activated Aurora A and the recruitment of the complex onto a TPX2-dependent scaffold. Our data identify TPX2 as the only direct RanGTP target and NEDD1 as the only Aurora A substrate essential for the activation of the RanGTP-dependent MT nucleation pathway.
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