ArticleCurrent biology : CB2013
Aurora B inhibits MCAK activity through a phosphoconformational switch that reduces microtubule association.
Article in Current biology : CB, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- KIF2C/MCAK a prognostic biomarker and its oncogenic potential in malignant progression, and prognosis of cancer patients: a systematic review and meta-analysis as biomarker.Critical reviews in clinical laboratory sciences · 2024Pooled it
- 45A ncRNA Expression Leads to Chromosomal Instability and Cytoskeletal Dynamics Impairment by Modulating GTSE1/p53/AurB Subcellular Localization.International journal of molecular sciences · 2026Article
- SAPCD2 phosphorylation modulates astral microtubule stability to control spindle orientation.Communications biology · 2026Article
- Microtubules guide Aurora B substrate geometries for accurate chromosome segregation.Science advances · 2026Article
- Physical Frameworks and Theories on How Autonomous Biological Oscillators Synchronize.Advances in experimental medicine and biology · 2026Review
- The Kinesin-14 tail: Dual microtubule binding domains drive spindle morphogenesis through tight microtubule cross-linking and robust sliding.Molecular biology of the cell · 2025Article
- Mechanism and regulation of kinesin motors.Nature reviews. Molecular cell biology · 2025Review
- Aurora-B: a novel biomarker in the invasion and metastasis of osteosarcoma.Biomarkers in medicine · 2024Review
- Article
- Importin α/β promote Kif18B microtubule association and enhance microtubule destabilization activity.Molecular biology of the cell · 2023Article
- Potent microtubule-depolymerizing activity of a mitotic Kif18b-MCAK-EB network.Journal of cell science · 2023Article
- Characterization of a recently synthesized microtubule-targeting compound that disrupts mitotic spindle poles in human cells.Scientific reports · 2021Article
- SCFThe EMBO journal · 2021Article
- Wnt signaling establishes the microtubule polarity in neurons through regulation of Kinesin-13.The Journal of cell biology · 2021Article
- Article
- Spatial regulation of MCAK promotes cell polarization and focal adhesion turnover to drive robust cell migration.Molecular biology of the cell · 2021Article
- Compromised MPS1 Activity Induces Multipolar Spindle Formation in Oocytes From Aged Mares: Establishing the Horse as a Natural Animal Model to Study Age-Induced Oocyte Meiotic Spindle Instability.Frontiers in cell and developmental biology · 2021Article
- A Guide to Fluorescence Lifetime Microscopy and Förster's Resonance Energy Transfer in Neuroscience.Current protocols in neuroscience · 2020Review
- RanGTP induces an effector gradient of XCTK2 and importin α/β for spindle microtubule cross-linking.The Journal of cell biology · 2020Article
- Clathrin's adaptor interaction sites are repurposed to stabilize microtubules during mitosis.The Journal of cell biology · 2020Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProper spindle assembly and chromosome segregation rely on precise microtubule dynamics, which are governed in part by the kinesin-13 MCAK. MCAK microtubule depolymerization activity is inhibited by Aurora B-dependent phosphorylation, but the mechanism of this inhibition is not understood.
resultsHere, we develop the first Förster resonance energy transfer (FRET)-based biosensor for MCAK and show that MCAK in solution exists in a closed conformation mediated by an interaction between the C-terminal domain (CT) and the neck. Using fluorescence lifetime imaging (FLIM) we show that MCAK bound to microtubule ends is closed relative to MCAK associated with the microtubule lattice. Aurora B phosphorylation at S196 in the neck opens MCAK conformation and diminishes the interaction between the CT and the neck. Using FLIM and TIRF imaging, we find that changes in MCAK conformation are associated with a decrease in MCAK affinity for the microtubule.
conclusionsUnlike motile kinesins, which are open when doing work, the high-affinity binding state for microtubule-depolymerizing kinesins is in a closed conformation. Phosphorylation switches MCAK conformation, which inhibits its ability to interact with microtubules and reduces its microtubule depolymerization activity. This work shows that the conformational model proposed for regulating kinesin activity is not universal and that microtubule-depolymerizing kinesins utilize a distinct conformational mode to regulate affinity for the microtubule, thus controlling their catalytic efficiency. Furthermore, our work provides a mechanism by which the robust microtubule depolymerization activity of kinesin-13s can be rapidly modulated to control cellular microtubule dynamics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.