Tubulin depolymerization may be an ancient biological motor

Abstract

SummaryThe motions of mitotic chromosomes are complex and show considerable variety across species. A wealth of evidence supports the idea that microtubule-dependent motor enzymes contribute to this variation and are important both for spindle formation and for the accurate completion of chromosome segregation. Motors that walk towards the spindle pole are, however, dispensable for at least some poleward movements of chromosomes in yeasts, suggesting that depolymerizing spindle microtubules can generate mitotic forces in vivo. Tubulin protofilaments that flare outward in association with microtubule shortening may be the origin of such forces, because they can move objects that are appropriately attached to a microtubule wall. For example, some kinetochore-associated proteins can couple experimental objects, such as microspheres, to shortening microtubules in vitro, moving them over many micrometers. Here, we review recent evidence about such phenomena, highlighting the force-generation mechanisms and different coupling strategies. We also consider bending filaments of the tubulin-like protein FtsZ, which form rings girding bacteria at their sites of cytokinesis. Mechanical similarities between these force-generation systems suggest a deep phylogenetic relationship between tubulin depolymerization in eukaryotic mitosis and FtsZ-mediated ring contraction in bacteria. Journal of Cell Scienceshortening can do work are now well developed, although there is disagreement on how tubulin depolymerization is coupled to its cargo. This Commentary summarizes aspects of recent studies on tubulin depolymerization and juxtaposes them with studies on the bacterial tubulin-like protein FtsZ. The results suggest that the mechanism by which tubulin polymers can exert force as they shorten is ancient and related to the machinery for bacterial cell cleavage. MT depolymerization is a motor in eukaryotic cellsHoyt and colleagues showed that mitosis can work in the budding yeast Saccharomyces cerevisiae with only two MT-dependent motors: a twofold symmetric, homo-tetrameric kinesin 5 that helps spindles to form; and a second motor that promotes tubulin depolymerizaton (Cottingham et al., 1999). Mitosis limped along well enough to sustain colony growth, even when cells contained only kinesin 5 and a mutated depolymerizing motor, so long as a drug was added to enhance MT depolymerization. However, these studies did not include direct observation of chromosome motions. More recent work from our laboratory has shown that, in the fission yeast Saccharomyces pombe, the deletion of all three minusend-directed MT-dependent motors (the ones that could pull a chromosome poleward) does not reduce the maximal speed of such motions ( Fig. 1) (Grishchuk and McIntosh, 2006). This result has been confirmed in budding yeast (Tanaka et al., 2007) and expanded in fission yeasts (Franco et al., 2007;Gachet et al., 2008), leading to the conclusion that minus-end-directed motors are dispensable for chromosome-to-pole motion in two rather distantly related...

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“…123 The force of microtubule plus-end depolymerization has a crucial role in generating the tension that pulls a chromatid from its sister. [124][125][126] In fact, in fission yeast, minus end-directed motor proteins are entirely dispensable for poleward motion of chromosomes -the force generated by microtubule depolymerization is sufficient. 127 Cortical Figure 3 Cooperation of cortical dynein with HSET.…”

Bacterial Tubulin Distinct Loop Sequences and Primitive Assembly Properties Support Its Origin from a Eukaryotic Tubulin Ancestor

“…All members of the tubulin/FtsZ family have a N-terminal GTP-binding domain and a GTPaseactivating domain, hypothesized to come from the fusion of two previously separate proteins that copolymerized forming protofilaments, thus linking nucleotide hydrolysis with polymerization (63). The common features of tubulin and FtsZ depolymerization suggest an ancient protofilament bending motor (64,65). At some point, gene duplication gave rise to a primitive ␣-and ␤-tubulin that assembled into heteropolymers with the GTP-binding site between monomers (Fig.…”

Long tethers provide high-force coupling of the Dam1 ring to shortening microtubules

“…When conjugated to microbeads, several kinetochore proteins can sustain processive motions at the ends of dynamic MTs (reviewed in ref. 6), but only a few have so far been reported to form force-transducing attachments (7)(8)(9)(10)(11). The average force that these proteins captured from MT disassembly was <5 pN.…”