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Review
. 2020 Jul 6;54(1):7-20.
doi: 10.1016/j.devcel.2020.06.008.

The Tubulin Code in Microtubule Dynamics and Information Encoding

Antonina Roll-Mecak  1
Affiliations
Review

The Tubulin Code in Microtubule Dynamics and Information Encoding

Antonina Roll-Mecak. Dev Cell. .

Abstract

Microtubules are non-covalent mesoscale polymers central to the eukaryotic cytoskeleton. Microtubule structure, dynamics, and mechanics are modulated by a cell's choice of tubulin isoforms and post-translational modifications, a "tubulin code," which is thought to support the diverse morphology and dynamics of microtubule arrays across various cell types, cell cycle, and developmental stages. We give a brief historical overview of research into tubulin diversity and highlight recent progress toward uncovering the mechanistic underpinnings of the tubulin code. As a large number of essential pathways converge upon the microtubule cytoskeleton, understanding how cells utilize tubulin diversity is crucial to understanding cellular physiology and disease.

Keywords: CCP; TTLL; detyrosination; dynein; glutamylation; glycylation; kinesin; microtubule; microtubule associated proteins; motors; severing; tubulin code; tubulin isoforms; tubulin post-translational modifications; tubulin tyrosine ligase; tyrosination.

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Figures

Figure 1.
Figure 1.. Microtubule structure and dynamics.
Microtubules are non-covalent cylindrical polymers assembled from 13 protofilaments formed by the head-to-tail addition of αβ-heterodimers. They grow by the addition of GTP-tubulin at their ends. Once incorporated into the microtubule, the GTP is hydrolyzed to GDP. Microtubules cycle between periods of growth and depolymerization. The transition from growth to depolymerization is called catastrophe. The transition from depolymerization to growth is called rescue. Microtubule dynamics are characterized by four parameters: rate of polymerization and depolymerization and frequency of catastrophe and rescue events.
Figure 2.
Figure 2.. Sequence variability among tubulin isoforms concentrates on the intrinsically disordered C-terminal tails and at polymerization interfaces.
(A) Molecular surface of three protofilaments from a microtubule showing lattice contacts of the central αβ-tubulin dimer within a microtubule. α- and β-tubulin colored as in Figure 1. Sequences from Homo sapiens α- and β-tubulin isoforms were aligned and conservative sequence substitutions mapped in magenta on the atomic model (PDB ID: 6dpu). The M-loop position is highlighted by a yellow ellipse. (B) Molecular surface of the αβ-tubulin dimer colored as in (A) illustrating the sequence variability on the C-terminal tails and lateral (between tubulin heterodimers in neighboring protofilaments) and longitudinal (between tubulin heterodimers within the same protofilament) polymerization interfaces.
Figure 3.
Figure 3.. αβ-tubulin dimers are functionalized with a diverse arrays of chemically distinct posttranslational modifications.
Schematic of a neuron (microtubules, blue; actin, pink) with a close-up of a microtubule decorated with diverse posttranslational modifications. Microtubule colored as in Figure 1. α-tubulin tyrosination, orange; monoglutamaylation, light red; polyglutamylation red; monoglycylation, light green; polyglycylation, green; acetylation or methylation on α-tubulin Lys40, magenta; phosphorylation on Ser172, yellow; polyamination, purple. Microtubule cross-section shows the luminal position of Lys40. Boxes show the chemical structure of selected posttranslational modifications. We note that the linkage of the polyglutamate chain is still not clear with studies reporting both α-linked glutamate chains (Redeker et al., 1991), shown here (where the elongating glutamate forms a peptide bond with the branch glutamate residue) and γ-linked chains (where the elongating glutamate forms an isopeptide bond with the branch glutamate residue (Wolff et al., 1994)).
Figure 4.
Figure 4.. The tubulin code regulates interactions with microtubule effectors
(A) Schematic of a neuron with microtubule and posttranslational modifications colored as in Figure 3. Insets show in clockwise direction, spastin recruited preferentially to glutamylated microtubules, CLIP170 and dynein-dynactin recruited to the plus ends of microtubules enriched in tyrosination, and dynein/dynactin-initiated motility at tyrosinated microtubule sections through the Cap-Gly domain in p150/dynactin; once initiated, motility is independent of the microtubule tyrosination status. (B) Schematic of the mitotic spindle with microtubule and posttranslational modifications colored as in Figure 3. Inset shows preferential recruitment of chromosome-associated CENP-E to detyrosinated microtubules. (C) Schematic of a flagellum with microtubules and posttranslational modifications colored as in Figure 3. Spheres denote cargo trains. Inset shows designated transport lanes on the microtubule doublet with kinesin anterograde trains running on the glutamylated, glycylated- and detyrosinated-enriched B-tubule and dynein retrograde trains running on the tyrosinated A-tubule.
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