A microtubule bestiary: structural diversity in tubulin polymers

Abstract

Microtubules are long, slender polymers of αβ-tubulin found in all eukaryotic cells. Tubulins associate longitudinally to form protofilaments, and adjacent protofilaments associate laterally to form the microtubule. In the textbook view, microtubules are 1) composed of 13 protofilaments, 2) arranged in a radial array by the centrosome, and 3) built into the 9+2 axoneme. Although these canonical structures predominate in eukaryotes, microtubules with divergent protofilament numbers and higher-order microtubule assemblies have been discovered throughout the last century. Here we survey these noncanonical structures, from the 4-protofilament microtubules of Prosthecobacter to the 40-protofilament accessory microtubules of mantidfly sperm. We review the variety of protofilament numbers observed in different species, in different cells within the same species, and in different stages within the same cell. We describe the determinants of protofilament number, namely nucleation factors, tubulin isoforms, and posttranslational modifications. Finally, we speculate on the functional significance of these diverse polymers. Equipped with novel tubulin-purification tools, the field is now prepared to tackle the long-standing question of the evolutionary basis of microtubule structure.

Human β-Tubulin Isotypes Can Regulate Microtubule Protofilament Number and Stability

“…Importantly, microtubules with a non-13 protofilaments (e.g. 14 or 15 protofilaments) have also been found in diverse cell types across different species (Chaaban and Brouhard, 2017). However, we do not understand how protofilament number is regulated.…”

“…Tubulin purified from animal brains, which has been extensively used for biochemical and structural analyses, contains a mixture of different tubulin isotypes (Banerjee et al, 1988) and polymerizes into microtubules containing 9 to 16 protofilaments in vitro (Chaaban and Brouhard, 2017). Recent studies have described the purification and use of recombinant human tubulin and have shown differences in polymerization dynamics of microtubules assembled with different β-tubulin isotypes (Pamula et al, 2016; Vemu et al, 2016).…”

Pseudo-repeats in doublecortin make distinct mechanistic contributions to microtubule regulation

“…MTs are built of /-tubulin heterodimers that assemble longitudinally into protofilaments (PFs) and laterally into hollow cylinders. In vitro, MTs can form with various PF numbers, but in mammalian cells they mainly contain 13 PFs (Chaaban and Brouhard, 2017;Tilney et al, 1973). DCX strongly promotes nucleation and stabilisation of this physiological 13-PF architecture (Moores et al, 2004).…”

Molecular modeling study on the differential microtubule‐stabilizing effect in singly‐ and doubly‐bonded complexes with peloruside A and paclitaxel

“…In living cells, stable MTs are mostly formed by the parallel arrangement of 13 PFs, whereas under laboratory conditions MTs ranging typically from 12 to 17 PFs can be obtained . The predominance of 13‐PF arrangements has been explained in the literature in terms of the “straight‐protofilament hypothesis,” which states that only the 13‐PF geometry allows PFs to run straight relative to the MT axis . As cytoskeletal components MTs exist in a continuously dynamic state of growing and shortening through the reversible association and dissociation of αβ‐tubulin heterodimers.…”

“…2 The predominance of 13-PF arrangements has been explained in the literature in terms of the "straight-protofilament hypothesis," which states that only the 13-PF geometry allows PFs to run straight relative to the MT axis. 3 As cytoskeletal components MTs exist in a continuously dynamic state of growing and shortening through the reversible association and dissociation of αβ-tubulin heterodimers. This dynamic behavior is controlled by the GTP/GDP exchange in the β-subunit of a MT end, while other GTP unit is tightly bound to α-tubulin and is nonexchangeable.…”