The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends
Abstract
The microtubule cytoskeleton is a dynamic structure in which the lengths of the microtubules are tightly regulated. One regulatory mechanism is the depolymerization of microtubules by motor proteins in the kinesin-13 family. These proteins are crucial for the control of microtubule length in cell division, neuronal development and interphase microtubule dynamics. The mechanism by which kinesin-13 proteins depolymerize microtubules is poorly understood. A central question is how these proteins target to microtubule ends at rates exceeding those of standard enzyme-substrate kinetics. To address this question we developed a single-molecule microscopy assay for MCAK, the founding member of the kinesin-13 family. Here we show that MCAK moves along the microtubule lattice in a one-dimensional (1D) random walk. MCAK-microtubule interactions were transient: the average MCAK molecule diffused for 0.83 s with a diffusion coefficient of 0.38 microm2 s(-1). Although the catalytic depolymerization by MCAK requires the hydrolysis of ATP, we found that the diffusion did not. The transient transition from three-dimensional diffusion to 1D diffusion corresponds to a "reduction in dimensionality" that has been proposed as the search strategy by which DNA enzymes find specific binding sites. We show that MCAK uses this strategy to target to both microtubule ends more rapidly than direct binding from solution.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Dwell times were corrected for photobleaching using the photobleaching time constant determined from the data.
“dwell times were calculated from dwell-time distributions (Figure S3) and corrected for photobleaching as described in [10] using the photobleaching time constant determined from the data shown in Figure S2E”
From In vitro reconstitution of the functional interplay between MCAK and EB3 at microtubule plus ends (2010) · cites this paper as [10]
Cites
Mechanics of Motor Proteins and the Cytoskeleton
Howard, & Clark (2002) · Applied Mechanics Reviews · doi:10.1115/1.1451234 · Cited by 2,909 · see citing works
Diffusion-driven mechanisms of protein translocation on nucleic acids. 1. Models and theory
Berg, O. G., Winter, R. B., & von Hippel, P. H. (1981) · Biochemistry · doi:10.1021/bi00527a028 · Cited by 1,305 · see citing works
How do site-specific DNA-binding proteins find their targets?
Halford, S. E. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh624 · Cited by 891 · see citing works
Movement of microtubules by single kinesin molecules
Howard, J., Hudspeth, A. J., & Vale, R. D. (1989) · Nature · doi:10.1038/342154a0 · Cited by 885 · see citing works
Self-citationThe lac represser-operator interaction
Riggs, A. D., Bourgeois, S., & Cohn, M. (1970) · Journal of Molecular Biology · doi:10.1016/0022-2836(70)90074-4 · Cited by 751 · see citing works
Kin I kinesins are microtubule-destabilizing enzymes
Desai, A., Verma, S., Mitchison, T. J., & Walczak, C. E. (1999) · Cell · doi:10.1016/s0092-8674(00)80960-5 · Cited by 708 · see citing works
Lac represser-operator interaction
Jobe, A. H., & Bourgeois, S. (1973) · Journal of Molecular Biology · doi:10.1016/0022-2836(73)90023-5 · Cited by 690 · see citing works
Winter, R. B., Berg, O. G., & von Hippel, P. H. (1981) · Biochemistry · doi:10.1021/bi00527a030 · Cited by 601 · see citing works
Microtubule dynamics and microtubule caps: a time-resolved cryo-electron microscopy study.
Mandelkow�, E., Mandelkow�, E., & Milligan, R. A. (1991) · The Journal of Cell Biology · doi:10.1083/jcb.114.5.977 · Cited by 574 · see citing works
Kinetics of protein-protein association explained by Brownian dynamics computer simulation.
Northrup, S. H., & Erickson, H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.8.3338 · Cited by 572 · see citing works
Walczak, C., Mitchison, T. J., & Desai, A. B. (1996) · Cell · doi:10.1016/s0092-8674(00)80991-5 · Cited by 534 · see citing works
Hunter, A., Caplow, M., Coy, D. L., Hancock, W., Diez, S., Wordeman, L., & Howard, J. (2003) · Molecules and Cells · doi:10.1016/s1097-2765(03)00049-2 · Cited by 404 · see citing works
Self-citationHyman, A. A., Salser, S. J., Drechsel, D. N., Unwin, N., & Mitchison, T. J. (1992) · Molecular Biology of the Cell · doi:10.1091/mbc.3.10.1155 · Cited by 399 · see citing works
Wordeman, L. G., & Mitchison, T. J. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.128.1.95 · Cited by 381 · see citing works
Diffusion controlled reaction rates in spheroidal geometry
Richter, P. H., & Eigen, M. (1974) · Biophysical Chemistry · doi:10.1016/0301-4622(74)80050-5 · Cited by 359 · see citing works
Tournebize, R., Popov, A. V., Kinoshita, K., Ashford, A. J., Rybina, S., Pozniakovsky, A., Mayer, T. U., Walczak, C., Karsenti, E., & Hyman, A. A. (1999) · Nature Cell Biology · doi:10.1038/71330 · Cited by 326 · see citing works
Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase
Rogers, G. C., Rogers, S. L., Schwimmer, T. A., Ems-McClung, S. C., Walczak, C., Vale, R. D., Scholey, J. M., & Sharp, D. J. (2003) · Nature · doi:10.1038/nature02256 · Cited by 317 · see citing works
Mitotic Centromere–associated Kinesin Is Important for Anaphase Chromosome Segregation
Maney, T., Hunter, A. W., Wagenbach, M., & Wordeman, L. G. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.3.787 · Cited by 289 · see citing works
Kinesin Superfamily Protein 2A (KIF2A) Functions in Suppression of Collateral Branch Extension
Homma, N., Takei, Y., Tanaka, Y., Nakata, T., Terada, S., Kikkawa, M., Noda, Y., & Hirokawa, N. (2003) · Cell · doi:10.1016/s0092-8674(03)00522-1 · Cited by 281 · see citing works
Engineering the Processive Run Length of the Kinesin Motor
Thorn, K. S., Ubersax, J. A., & Vale, R. D. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.5.1093 · Cited by 275 · see citing works
Kinesin ATPase: rate-limiting ADP release
Hackney, D. D. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.17.6314 · Cited by 239 · see citing works
KIF1A Alternately Uses Two Loops to Bind Microtubules
Nitta, R., Kikkawa, M., Okada, Y., & Hirokawa, N. (2004) · Science · doi:10.1126/science.1096621 · Cited by 200 · see citing works
Interaction of brain cytoplasmic dynein and MAP2 with a common sequence at the C terminus of tubulin
Paschal, B. M., Obar, R. A., & Vallée, R. (1989) · Nature · doi:10.1038/342569a0 · Cited by 178 · see citing works
The C-Terminus of Tubulin Increases Cytoplasmic Dynein and Kinesin Processivity
Wang, Z., & Sheetz, M. P. (2000) · Biophysical Journal · doi:10.1016/s0006-3495(00)76743-9 · Cited by 164 · see citing works
Mennella, V., Rogers, G. C., Rogers, S. L., Buster, D. W., Vale, R. D., & Sharp, D. J. (2005) · Nature Cell Biology · doi:10.1038/ncb1222 · Cited by 154 · see citing works
Maney, T., Wagenbach, M., & Wordeman, L. G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106626200 · Cited by 150 · see citing works
A Mechanism for Microtubule Depolymerization by KinI Kinesins
Moores, C. A., Yu, M., Guo, J., Béraud, C., Sakowicz, R., & Milligan, R. A. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00503-8 · Cited by 146 · see citing works
K-loop insertion restores microtubule depolymerizing activity of a “neckless” MCAK mutant
Ovechkina, Y., Wagenbach, M., & Wordeman, L. G. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200205089 · Cited by 102 · see citing works
XKCM1 acts on a single protofilament and requires the C terminus of tubulin
Niederstrasser, H., Salehi-Had, H., Gan, E. C., Walczak, C., & Nogales, E. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5360 · Cited by 73 · see citing works
Filament Depolymerization by Motor Molecules
Klein, G. A., Kruse, K., Cuniberti, G., et al. (2005) · Physical Review Letters · doi:10.1103/physrevlett.94.108102 · Cited by 61 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Tracking the ends: a dynamic protein network controls the fate of microtubule tips
Akhmanova, A., & Steinmetz, M. O. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2369 · Cited by 1,047 · see citing works
Traffic control: regulation of kinesin motors
Verhey, K. J., & Hammond, J. W. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2782 · Cited by 546 · see citing works
Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner
Varga, V., Helenius, J., Tanaka, K., Hyman, A. A., Tanaka, T. U., & Howard, J. (2006) · Nature Cell Biology · doi:10.1038/ncb1462 · Cited by 445 · see citing works
Self-citationA minimal midzone protein module controls formation and length of antiparallel microtubule overlaps
Bieling, P., Telley, I. A., & Surrey, T. (2010) · Cell · doi:10.1016/j.cell.2010.06.033 · Cited by 326 · see citing works
Kinesin Motor Mechanics: Binding, Stepping, Tracking, Gating, and Limping
Block, S. M. (2007) · Biophysical Journal · doi:10.1529/biophysj.106.100677 · Cited by 338 · see citing works
He, M., Subramanian, R., Bangs, F., Omelchenko, T., Liem Jr, K. F., Kapoor, T. M., & Anderson, K. V. (2014) · Nature Cell Biology · doi:10.1038/ncb2988 · Cited by 302 · see citing works
Microtubule polymerases and depolymerases
Howard, J., & Hyman, A. A. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.12.009 · Cited by 294 · see citing works
Self-citationThe mitotic kinesin-14 Ncd drives directional microtubule–microtubule sliding
Fink, G., Hajdo, L., Skowronek, K. J., Reuther, C., Kasprzak, A. A., & Diez, S. (2009) · Nature Cell Biology · doi:10.1038/ncb1877 · Cited by 226 · see citing works
Self-citationAurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E
Kim, Y., Holland, A. J., Lan, W., & Cleveland, D. W. (2010) · Cell · doi:10.1016/j.cell.2010.06.039 · Cited by 233 · see citing works
Molecular Basis for Age-Dependent Microtubule Acetylation by Tubulin Acetyltransferase
Szyk, A., Deaconescu, A. M., Spector, J., Goodman, B., Valenstein, M. L., Ziolkowska, N. E., Kormendi, V., Grigorieff, N., & Roll-Mecak, A. (2014) · Cell · doi:10.1016/j.cell.2014.03.061 · Cited by 218 · see citing works
Tanenbaum, M. E., Macurek, L., van der Vaart, B., Galli, M., Akhmanova, A., & Medema, R. H. (2011) · Current Biology · doi:10.1016/j.cub.2011.07.017 · Cited by 148 · see citing works
In vitro reconstitution of the functional interplay between MCAK and EB3 at microtubule plus ends
Montenegro Gouveia, S., Leslie, K., Kapitein, L. C., Buey, R. M., Grigoriev, I., Wagenbach, M., Smal, I., Meijering, E., Hoogenraad, C. C., Wordeman, L., et al. (2010) · Current Biology · doi:10.1016/j.cub.2010.08.020 · Cited by 147 · see citing works
Microtubule cross-linking triggers the directional motility of kinesin-5
Kapitein, L. C., Kwok, B. H., Weinger, J. S., Schmidt, C. F., Kapoor, T. M., & Peterman, E. J. G. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200801145 · Cited by 143 · see citing works
Aurora A phosphorylates MCAK to control ran-dependent spindle bipolarity
Zhang, X., Ems-McClung, S. C., & Walczak, C. E. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-02-0198 · Cited by 123 · see citing works
Kif18B interacts with EB1 and controls astral microtubule length during mitosis
Stout, J. R., Yount, A. L., Powers, J. A., LeBlanc, C., Ems-McClung, S. C., & Walczak, C. E. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-04-0363 · Cited by 111 · see citing works
Allosteric inhibition of kinesin-5 modulates its processive directional motility
Kwok, B. H., Kapitein, L. C., Kim, J. H., Peterman, E. J. G., Schmidt, C. F., & Kapoor, T. M. (2006) · Nature Chemical Biology · doi:10.1038/nchembio812 · Cited by 108 · see citing works
A nonmotor microtubule binding site in kinesin-5 is required for filament crosslinking and sliding
Weinger, J. S., Qiu, M., Yang, G., & Kapoor, T. M. (2011) · Current Biology · doi:10.1016/j.cub.2010.12.038 · Cited by 100 · see citing works
Furuta, K., & Toyoshima, Y. Y. (2008) · Current Biology · doi:10.1016/j.cub.2007.12.056 · Cited by 102 · see citing works
Cooper, J. R., Wagenbach, M., Asbury, C. L., & Wordeman, L. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1728 · Cited by 95 · see citing works
Lucky 13-microtubule depolymerisation by kinesin-13 motors
Moores, C. A., & Milligan, R. A. (2006) · Journal of Cell Science · doi:10.1242/jcs.03224 · Cited by 92 · see citing works
Mechanism and regulation of kinesin motors.
Yildiz, A. (2025) · Nature reviews. Molecular cell biology · doi:10.1038/s41580-024-00780-6 · Cited by 88 · see citing works
Ems-McClung, S. C., Hainline, S. G., Devare, J., Zong, H., Cai, S., Carnes, S. K., Shaw, S. L., & Walczak, C. E. (2013) · Current Biology · doi:10.1016/j.cub.2013.10.054 · Cited by 73 · see citing works
Lee, T., Langford, K. J., Askham, J. M., Brüning-Richardson, A., & Morrison, E. E. (2008) · Oncogene · doi:10.1038/sj.onc.1210867 · Cited by 69 · see citing works
All Wired Up: An Exploration of the Electrical Properties of Microtubules and Tubulin
Kalra, A. P., Eakins, B. B., Patel, S. D., Ciniero, G., Rezania, V., Shankar, K., & Tuszynski, J. A. (2020) · ACS Nano · doi:10.1021/acsnano.0c06945 · Cited by 49 · see citing works
- Authors
- Helenius, J., Brouhard, G., Kalaidzidis, Y., Diez, S., & Howard, J.
- Affiliations
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- Lomonosov Moscow State University (RU)
- Corresponding author
- Howard, Jonathon
- Venue
- Nature
- Published
- 2006-05
- Volume
- 441
- Issue
- 7089
- Pages
- 115-119
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2137262057
- Cited by
- 454
- References
- 30
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 8 · 2023: 16 · 2022: 15 · 2021: 18 · 2020: 15 · 2019: 20 · 2018: 24 · 2017: 23 · 2016: 27 · 2015: 23 · 2014: 28 · 2013: 25 · 2012: 28
- FWCI
- 13.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- MCAK, kinesin-13, microtubule depolymerization, microtubule ends, volume diffusion, one-dimensional random walk, microtubule length regulation, single-molecule microscopy, ATP hydrolysis, microtubule lattice
- MeSH terms
- Adenosine Triphosphate, Diffusion, Humans, Hydrolysis, Kinetics, Microtubules, Models, Biological, Substrate Specificity, Kinesins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review