POST-TRANSLATIONAL MODIFICATIONS a Chromosome’S Guide Simon Bradbrook/NPG to the Spindle Equator

RESEARCH HIGHLIGHTS

Nature Reviews Molecular Cell Biology | AOP, published online 13 May 2015; doi:10.1038/nrm4000

POST-TRANSLATIONAL MODIFICATIONS A chromosome’s guide Simon Bradbrook/NPG to the spindle equator

Accurate chromosome segregation to that observed following inhibition during mitosis requires that chromo- of CENP-E, indicating that spindle detyrosinated somes bi-orient; that is, that their cen- microtubule detyrosination is required microtubules tromeres attach to microtubules that for transport to the cell equator. form emanate from opposite ends of a bipo- Moreover, inhibition of detyro preferential lar spindle. Bi-orientation is achieved sination induced dissociation of more efficiently if chromosomes are CENP-E from microtubules, sug- tracks ... along aligned at the spindle equator. For this gesting that detyrosination promotes which CENP-E alignment to occur, chromosomes are CENP-E–microtubule interactions transports transported from near spindle poles to in vivo. the equator through a process known To test whether detyrosination chromosomes as chromosome congression. affects CENP-E directly, the authors How chromosomes are guided reconstituted CENP-E motility in vitro specifically to the equator during con- using purified tubulin from HeLa gression has been unclear. Barisic et al. cells. Although CENP-E bound and now report that transport by the moved processively on both tyrosi- kinesin motor centromere-associated nated and detyrosinated microtubules, protein E (CENP-E; also known as it was faster and achieved longer kinesin 7) to the spindle equator of runs on detyrosinated microtubules. human cells depends on microtubule Moreover, by measuring the force detyrosination, which consists of produced by single CENP-E motors the removal of the carboxy-terminal using a stationary optical trap, the tyrosine from α-tubulin. authors found that CENP-E generated During congression, chromosomes greater forces on detyrosinated micro- are first transported along micro tubules. Furthermore, CENP-E was tubules to the spindle poles by dynein seen to detach less frequently from and then to the equator by CENP-E, detyrosinated microtubules, indicat- which is a motor that walks towards ing that it can carry larger cargoes on microtubule plus ends. As the plus detyrosinated microtubule tracks. ends of microtubules that emanate Together, these results suggest from the poles point in different that detyrosinated microtubules form directions, including towards the cell preferential tracks from the poles to cortex, the cause of the directional- the cell equator, along which CENP-E ity of CENP-E-mediated transport transports chromosomes. Consistent towards the equator remained unclear. with this model, the authors found Tubulin acetylation and detyrosi- that abnormal detyrosination of nation, which are known to regulate microtubules, other than those point- transport in neurons, are found on ing to the equator, caused delivery stable spindle microtubules that point of pole-proximal chromosomes to to the equator. Whereas acetylation inappropriate locations. had no effect on chromosome con- This work adds to the growing gression in human U2OS cells, the body of evidence that post- authors found that overexpression of translational modifications can the enzyme responsible for α-tubulin contribute to the subcellular tyrosination, combined with a treat- differentiation of microtubules. ment that prevents detyrosination of Kim Baumann

polymerized α-tubulin, resulted in ORIGINAL RESEARCH PAPER Barisic, M. et al. delayed mitotic progression and the Microtubule detyrosination guides chromosomes misalignment of pole-proximal chro- during mitosis. Science http://dx.doi.org.10.1126/ science.aaa5175 (2015) mosomes. This phenotype was similar

NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 16 | JUNE 2015