For the best experience on the Abcam website please upgrade to a modern browser such as Google Chrome

We use cookies to make our site as useful as possible.

Our Cookie Policy explains how you can opt-out of the cookies we use.

If you continue without changing your cookie settings, we'll assume you’re happy with this.

Continue Continue

United States
Your country/region is currently set to:

If incorrect, please enter your country/region into the box below, to view site information related to your country/region.

Call (888) 77-ABCAM (22226) or contact us
Need help? Contact us

  • My account
  • Sign out
Sign in or Register with us

Welcome

Sign in or

Don't have an account?

Register with us
My basket
Quick order
Abcam homepage

  • Research Products
    By product type
    Primary antibodies
    Secondary antibodies
    ELISA and Matched Antibody Pair Kits
    Cell and tissue imaging tools
    Cellular and biochemical assays
    Proteins and Peptides
    By product type
    Proteomics tools
    Agonists, activators, antagonists and inhibitors
    Cell lines and Lysates
    Multiplex miRNA assays
    Multiplex Assays
    By research area
    Cancer
    Cardiovascular
    Cell Biology
    Epigenetics
    Metabolism
    Developmental Biology
    By research area
    Immunology
    Microbiology
    Neuroscience
    Signal Transduction
    Stem Cells
  • Diagnostic & Therapeutic Solutions
    Custom solutions & partnerships

    Custom antibody development and commercial partnerships to advance your diagnostic and therapeutic discovery.

    Create custom solutions with us

    Partner with us

  • Support
    Support hub

    Access advice and support for any research roadblock

    View support hub

    Protocols

    Your experiments laid out step by step

    View protocols

  • Events
    • Conference calendar
    • Cancer
    • Cardiovascular
    • Epigenetics & Nuclear signaling
    • Immunology
    • Neuroscience
    • Stem cells
    • Tradeshows
    • Scientific webinars
    Keep up to date with the latest events

    Full event breakdown with abstracts, speakers, registration and more

    View global event calendar

  • Pathways
    Cell signalling pathways

    View all pathways

    View all interactive pathways

Supporting our customers and employees during the COVID-19 pandemic. Read more

Microtubule structure and dynamics

Related

  • Read about cell cycle and download the pathway card
    • Browse the tubulin product catalog
      • See all microtubule-destabilizing agents available
        • Get advice from our small molecule inhibitor guide

          By Seán Mac Fhearraigh

          [Please note, this page is no longer updated]

          Microtubules are key components of the cytoskeleton, are composed of α-tubulin and β-tubulin and dimerize in a head to tail fashion to form linear protofilaments that associate initially into sheets and subsequently into hollow tubeswith a diameter of roughly 25 nm (1).


          Each Microtubule is composed of 13 protofilaments of α-tubulin and β-tubulin heterodimers. Microtubules are highly dynamic polymers that continuously grow and shrink during interphase and mitosis, with the rate of microtubule polymerisation to depolymerisation called the ‘catastrophe rate’ (2). In many cell types, the microtubule network organises in a radial manner, with the minus end of the microtubule embedded close to nucleus and the positive end exploring the cytoplasm (1). During microtubule polymerisation GTP-loaded β-tubulin is added to the plus end of the microtubule. Shortly after the addition GTP is hydrolysed to GDP. Stabilisation of microtubules requires the maintenance of a GTP-bound β-tubulin ‘cap’ to prevent depolymerisation. Removal of the ‘cap’ results in GDP-bound tubulin subunits adopting a curved conformation, the breaking of lateral bonds and microtubule catastrophe (1).

          Microtubules are required for the accurate separation of chromosomes during mitosis and the maintenance of genetic integrity. During mitosis microtubules form the mitotic spindle through the formation of a bipolar array of microtubules emanating from the centrosomes or the spindle pole body (3). During prometaphase microtubules emanate from the microtubule organising centres (MTOCs) and extend and shorten until they become amphitelically attached to chromosomes at their kinetochores. Activation of the spindle assembly checkpoint (SAC) during prometaphase prevents cells transitioning to anaphase until correct bipolar attachment of microtubules to chromosome kinetochores occurs (4). However, if the correct microtubule kinetochore attachment is not achieved in a timely manner due to monotelic, syntelic or merotelic attachment of microtubules to kinetochores, the cells arrest in pro-metaphase/metaphase-like state. Failure to resolve defective microtubule-kinetochore attachment can eventually result in cell death (5). 

          Completion of metaphase and the onset of anaphase occur following satisfaction of the SAC following correct attachment of microtubules to chromosomes. Finally, during anaphase chromosomes are distributed evenly to polar spindles, allowing each daughter cell to receive the correct genomic information.


          Microtubule targeting agents (MTAs)

          Taxol (Paclitaxel) was originally isolated from the bark of a yew tree (Taxus brevifola) by Monroe Wall and Mansukh Wani in 1967 (6). Taxol was approved for clinical use in 1995 and is now used to treat a range of malignancies such as breast cancer, kaposi’s sarcoma, ovarian cancer and non small cell lung cancer (7). Taxol binds tubulin heterodimers with a 1:1 stoichiometry along the surface of microtubules, thus, stabilising microtubules and resulting in microtubule bundle formation (8,9)

          Due to the highly dynamic nature of microtubules and the key regulatory roles they play in mitosis, compounds that alter microtubule function have been highly successful in cancer treatment. Microtubule targeting agents can be divided into two main groups based on their ability to depolymerise or hyperpolymerise microtubule filaments. Such families of compounds include the taxanes and the vinca alkaloids which were first identified over 40 years ago and members of both drug families are currently in clinical use to treat a range of cancers (7).

          The microtubule depolymerising agents, which are capable of inhibiting microtubule polymerisation at high concentrations, include members of the vinca alkaloid family vincristine, vinblastine, vindesine, colchicines, combrestatins and nocodazole. Microtubule destabilisation by depolymerising agents occurs through the binding of the drugs to either the vinca domain or the colchicine domain of β-tubulin, resulting in the inhibition of microtubule dynamics and the destruction of the mitotic spindle (6). 

          The suppression of microtubule dynamics by MTAs results in the inhibition of microtubule spindle formation, kinetochore-microtubule attachment and prevents chromosome bi-orientation. This in turn leads to the activation of the SAC, prolonged mitotic arrest and subsequent cell death (10). However, to date the link between prolonged mitotic arrest and the initiation of cell death is poorly understood.


          References

          • 1. Plus-end-tracking proteins and their interactions at microtubule ends. Galjart N. [Curr Biol. 2010;20(12):R528-37]
          • 2. Cell biology. Microtubule catastrophe. McIntosh JR. [Nature. 1984;312(5991):196-7]
          • 3. Cell biology. A gradient signal orchestrates the mitotic spindle. Clark PR. [Science. 2005;309(5739):1334-5]
          • 4. The spindle-assembly checkpoint in space and time. Musachio A, Salmon ED. [Nat Rev Mol Cell Biol. 2007;8(5):379-93]
          • 5. Cyclin B1 interacts with the BH3-only protein Bim and mediates its phosphorylation by Cdk1 during mitosis. Mac Fhearraigh S, Mc Gee MM. [Cell Cycle. 2011;10(22):3886-96]
          • 6. Microtubules as a target for anitcancer drugs. Jordan MA, Wilson L. [Nat Rev Cancer. 2004;4(4):253-65]
          • 7. Microtubule-binding agents: a dynamic field of cancer therapeutics. Dumontet C, Jordan A. [Nat Rev Drug Discov. 2010;9(10):790-803]
          • 8. Resistance to Taxol in lung cancer cells associated with increased microtubule dynamics. Gonçalves A, Braguer D, Kamath K, Martello L, Briand C, Horwitz S, Wilson L, Jordan MA. [Proc Natl Acad Sci USA. 2001;98(20):11737-42]
          • 9. Structure of tubulin at 6.5 A and location of the taxol-binding site. Nogales E, Wolf SG, Khan IA, Ludueña RF, Downing KH. [Nature. 1995;375(6530):424-7]
          • 10. Cancer cells display profound intra and interline variation following prolonged exposure to antimitotic drugs. Gascoigne KE, Taylor SS. [Cancer Cell. 2008;14(2):111-22]
          Get resources and offers direct to your inbox Sign up
          A-Z by research area
          • Cancer
          • Cardiovascular
          • Cell biology
          • Developmental biology
          • Epigenetics & Nuclear signaling
          • Immunology
          • Metabolism
          • Microbiology
          • Neuroscience
          • Signal transduction
          • Stem cells
          A-Z by product type
          • Primary antibodies
          • Secondary antibodies
          • Biochemicals
          • Isotype controls
          • Flow cytometry multi-color selector
          • Kits
          • Loading controls
          • Lysates
          • Peptides
          • Proteins
          • Slides
          • Tags and cell markers
          • Tools & Reagents
          Help & support
          • Support
          • Make an Inquiry
          • Protocols & troubleshooting
          • Placing an order
          • RabMAb products
          • Biochemical product FAQs
          • Training
          • Browse by Target
          Company
          • Corporate site
          • Investor relations
          • Company news
          • Careers
          • About us
          • Blog
          Events
          • Tradeshows
          • Conferences
          International websites
          • abcam.cn
          • abcam.co.jp

          Join with us

          • LinkedIn
          • facebook
          • Twitter
          • YouTube
          • Terms of sale
          • Website terms of use
          • Cookie policy
          • Privacy policy
          • Legal
          • Modern slavery statement
          © 1998-2021 Abcam plc. All rights reserved.