Cited by 454Microtubule and mitosis dynamicsDiffusion and Search DynamicsAdvanced Fluorescence Microscopy Techniques

The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends

Helenius, Jonne, Brouhard, Gary, Kalaidzidis, Yannis, Diez, Stefan, Howard, Jonathon·2006·Nature

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.

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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
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

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