Just when you think the mitotic spindle can’t get any more magical, the Ran pathway comes out and says, “I’m here, beyotch!” Today’s image is from a paper showing how kinetochore fibers are stabilized using a Ran-dependent mechanism.
The mitotic spindle is a complicated apparatus that functions to separate chromosomes during mitosis through the attachment of microtubules to kinetochores on chromosomes. Many of these microtubules are sourced from a pair of centrosomes on either side of the spindle, but there is a population of important microtubules that are not generated at centrosomes. These “acentrosomal” microtubules are instead generated by the presence of RanGTP around the chromosomes. The idea is that these microtubules are able to capture kinetochores easily by being nucleated so close to them. The other ends (minus ends) of these acentrosomal microtubules are focused near the centrosomes, and a recent paper describes how these microtubules are stabilized. A protein called MCRS1 is a RanGTP-regulated protein and is found at the minus ends of chromosomal and kinetochore microtubules, according to Meunier and Vernos. MCRS1 stabilizes kinetochore fiber microtubules, and without it, spindles are unstable. As seen in the images above, MCRS1 (middle row, green in merged) is localized to the minus ends of microtubules (top row, red in merged). MCRS1 localization is more obvious (arrow in higher mag image) when only kinetochore fiber microtubules are present (middle column) when compared with control (left column). When kinetochore fibers are absent (right column), so is MCRS1.
Meunier, S., & Vernos, I. (2011). K-fibre minus ends are stabilized by a RanGTP-dependent mechanism essential for functional spindle assembly Nature Cell Biology, 13 (12), 1406-1414 DOI: 10.1038/ncb2372
Adapted by permission from Macmillan Publishers Ltd, copyright ©2011