The Tubulin Code: A Navigation System for Chromosomes during Mitosis

Successful congression of all chromosomes to establish a metaphase plate relies on the coordinated action of microtubule-based motor proteins with opposite activities. The mitotic spindle is made of anisotropic microtubules that accumulate distinct tubulin PTMs. Tubulin PTMs are part of the tubulin code, which is read by microtubule-associated proteins and motors, accounting for specific microtubule-based functions. Current models of motor-assisted chromosome motion do not take into account the contribution of tubulin PTMs. However, recent works support that kinetochore motors with opposite activities selectively distinguish the (de)tyrosination state of microtubules. Specific tubulin PTMs associated with distinct spindle microtubule subpopulations might work as a navigation system for kinetochore-based chromosome motility during mitosis. Before chromosomes segregate during mitosis in metazoans, they align at the cell equator by a process known as chromosome congression. This is in part mediated by the coordinated activities of kinetochore motors with opposite directional preferences that transport peripheral chromosomes along distinct spindle microtubule populations. Because spindle microtubules are all made from the same α/β-tubulin heterodimers, a critical longstanding question has been how chromosomes are guided to specific locations during mitosis. This implies the existence of spatial cues/signals on specific spindle microtubules that are read by kinetochore motors on chromosomes and ultimately indicate the way towards the equator. Here, we discuss the emerging concept that tubulin post-translational modifications (PTMs), as part of the so-called tubulin code, work as a navigation system for kinetochore-based chromosome motility during early mitosis. Before chromosomes segregate during mitosis in metazoans, they align at the cell equator by a process known as chromosome congression. This is in part mediated by the coordinated activities of kinetochore motors with opposite directional preferences that transport peripheral chromosomes along distinct spindle microtubule populations. Because spindle microtubules are all made from the same α/β-tubulin heterodimers, a critical longstanding question has been how chromosomes are guided to specific locations during mitosis. This implies the existence of spatial cues/signals on specific spindle microtubules that are read by kinetochore motors on chromosomes and ultimately indicate the way towards the equator. Here, we discuss the emerging concept that tubulin post-translational modifications (PTMs), as part of the so-called tubulin code, work as a navigation system for kinetochore-based chromosome motility during early mitosis. the process occurring during prometaphase of mitosis that accounts for the alignment of chromosomes to form a metaphase plate at the spindle equator. Immature and highly unstable configuration in which only one kinetochore from the pair is end-on attached to microtubules from a single spindle pole. Forces resulting from the direct action of polymerizing astral microtubules over chromatin (pushing force), and the action of the microtubule plus-end-directed chromokinesins located on chromosome arms (pulling force), that lead to the random ejection of chromosomes away from mitotic spindle poles. Erroneous configuration in which both sister kinetochores are attached to microtubules from the same spindle pole. If not corrected, this configuration would contribute to chromosome missegregation during mitosis. Enzymatic modification of tubulin through the attachment of one acetyl group to α- and/or β-tubulin. The most widely characterized acetylation event is the one involving K40 of α-tubulin, which faces the microtubule lumen and is mediated by the specific acetyltransferase αTat1. Several tubulin deacetylases (e.g., HDAC6 and Sirt2) have been reported to counteract the activity of αTat1. Acetylation of K40 of α-tubulin is normally associated with stable microtubules. Other acetylation events have been reported, but remain to be functionally characterized. Combination of tubulin isotypes and PTMs that generate microtubule diversity in cells and is expected to translate into variations of intrinsic microtubule properties and to be read by MAPs and motors to account for different microtubule-based functions in space and time. Enzymatic removal of the last tyrosine residue from the α-tubulin C-terminal tail on specific subsets of polymerized microtubules. Tubulin detyrosination is mediated by a yet unidentified TCP and reversed by a specific TTL. Enzymes that predominantly introduce PTMs on tubulin and microtubules, but some also modify other substrates. Enzymatic modification of tubulin through the generation of polyglutamate side chains on specific glutamate residues in the C-terminal tail of both α- and β-tubulin.