Tubulin and Microtubules


Microtubules are found in almost all types of eukaryotic cell. Their principal constituents are the highly conserved proteins of the tubulin family, in the form of longitudinal protofilaments of tubulin heterodimers. The conserved lateral interactions produce a characteristic 2D lattice. Tubulin structure and conformational changes are now known to atomic resolution. Its GTP‐dependent dynamic self‐assembly and disassembly is modulated by a host of other proteins. This dynamic activity and a more passive role as tracks for interaction with motor proteins, kinesin and dynein, allow microtubules to perform vital roles in various forms of cell motility. They are an essential component of cell division, provide oriented tracks for the transport of cellular organelles and vesicles and are responsible for the relative positioning of cellular compartments. Thus, they are important targets in the control of cancer cells, as their essential activity is severely affected by a variety of drugs.

Key Concepts

  • Tubulin heterodimers, consisting of highly homologous α‐ and β‐tubulin monomers, self‐assemble into a unique lattice with polar longitudinal ‘protofilaments’
  • The assembled sheet has a slightly variable curvature, producing microtubules, with around 13 protofilaments but not strictly defined unless they are grown from a γ‐tubulin template or given a curvature appropriate to exactly 13 protofilaments by accessory proteins
  • The structure of microtubules has been solved to near‐atomic level both with GTP homologues bound to β‐tubulin and with GDP bound; also a depolymerised protofilament structure in a longitudinally curved conformation is known
  • Hydrolysis of bound GTP enables microtubules to assemble with ‘dynamic instability’, behaviour that depends on stochastic disassembly when the GTP ‘cap’ is lost from a growing end
  • Microtubule behaviour is modified by many different accessory proteins that may act just at the tips or everywhere on the lattice wall
  • To play different roles according to their positions in cells, the properties of microtubules may vary owing to different tubulin isotypes and be modified by a wide range of associated proteins
  • Changes can also vary with time (‘ageing’) as a result of post‐translational modification of tubulin and of some accessory proteins
  • Microtubules are employed in axonemes of cilia and flagella, where the motor protein dynein interacts with them to produce beating while other linking components help control the wave‐form
  • Cytoplasmic microtubules provide tracks for vesicles and other cargoes driven by kinesins and cytoplasmic dynein
  • Mitotic and meiotic spindles are assembled from microtubules, which interact with kinetochores and with multiple motor proteins
  • Microtubules are susceptible to many small molecules that depolymerise or hyperstabilise them and thus serve as anti‐cancer drugs.

Keywords: dynamic instability; motility; microtubule lattices; GTP hydrolysis

Figure 1. (a,b) Microtubules in cells viewed by immunofluorescence light microscopy. DNA is labelled in blue, all microtubules in green, and glutamylated tubulin in red. The central spindle of the cell in anaphase (a) and the midbody microtubules between cells in the final stage of division (b) appear yellow (green plus red), where the tubulin is more modified. (c) A single microtubule as seen by cryo‐electron microscopy. (a,b) Courtesy of Dr Carsten Janke. (c) Taken by Dr Keiko Hirose.
Figure 2. Structure of microtubules. (a) Atomic structure of the αβ‐tubulin heterodimer (PDB code 1JFF) shown as a ribbon diagram; GTPase domains in red, intermediate/activation domains in blue, ‐terminal/outer‐surface domains in green, and central helices in yellow. (b) Assembly of heterodimers into longitudinal protofilaments, which in turn associate into sheets and microtubules. Side‐to‐side association of the protofilaments in two possible ways can produce an A‐lattice (symmetrical for the 13‐protofilament microtubule shown) or a B‐lattice (with an A‐lattice‐like seam for 13 or 14 protofilaments, though not for 15 or 16). (c) Typical features of the two ends of a microtubule. The minus ends cells are mostly capped by a γ‐tubulin ring complex that provides a template for the growth of 13 protofilaments. The plus ends often remain free to grow by addition of heterodimers to sites with GTP bound on the exposed β‐tubulin and shrink by loss of subunits that have caused GTP‐hydrolysis.
Figure 3. Structural changes in protofilaments. (a) αβ‐tubulin heterodimers as viewed from inside a microtubule. The two globular domains in each subunit are coloured red (GTPase) and blue; GDP, bound to the GTPase domains, is shown as space‐filling atoms (grey). The globular domains are separated by the core helix (yellow); Taxol binds in an adjacent pocket, where it promotes the straight conformation. The M‐loops make lateral contact with loops in the GTPase domains of another protofilament. At an active interface within a protofiilament, the T7 loop of α‐tubulin triggers GTP hydrolysis between heterodimers. The spacing there is greater when GTP is present than it is after hydrolysis, when loops around the nucleotide change conformation. The passive intra‐dimer interface does not change. (b) Stathmin (in grey) binds to two tubulin heterodimers in a curved conformation, in which there is bending at the passive and active interfaces. The binding sites are shown of some drugs (colchicine and vinblastine) that promote curvature and hence depolymerisation. Stathmin sequesters heterodimers to reduce the concentration of tubulin available for assembly.
Figure 4. Diagrams showing how the orientations of microtubules vary during the cell cycle. (a) A typical motile cell, such as a fibroblast, in interphase. Most microtubules grow out towards the cell periphery keeping their minus ends associated with the centrosomal region. This structure contains a pair of centrioles surrounded by a cloud of proteins that include γ‐tubulin. The plus ends grow out dynamically, with specific proteins tracking the microtubule tips. These may interact eventually with specific membrane‐associated proteins or with the cortical layer of actin filaments (yellow). See also: Cell Locomotion (b) Vertebrate mitotic spindle depicted in metaphase (chromosomes paired at the mid‐plane of the spindle) and in anaphase (chromosomes moving towards the poles). The centrosome at each pole, containing one old and one new centriole, acts as a focus for microtubule minus ends.
Figure 5. (a) Cross section through a typical axoneme, viewed from the tip, that is, from the plus ends of the microtubules. Microtubules were first seen in flagellar and ciliary axonemes. (b) Enlarged cross section of one of the doublet microtubules. Nine doublet microtubules and a central core structure are linked together by a complex variety of accessory molecules. Centrioles (Figure) are built from nine triplet microtubules, with a C‐microtubule attached to each B‐microtubule; their A tubules do not have dynein arms attached.


Al‐Bassam J and Chang F (2011) Regulation of microtubule dynamics by TOG‐domain proteins XMAP215/Dis1 and CLASP. Trends in Cell Biology 21: 604–614.

Alushin GM, Lander GC, Kellogg EH, et al. (2014) High‐resolution microtubule structures reveal the structural transitions in αβ‐tubulin upon GTP hydrolysis. Cell 157: 1117–1129.

Amos LA and Klug A (1974) Arrangement of subunits in flagellar microtubules. Journal of Cell Science 14: 523–549.

Amos LA and Schlieper D (2005) Microtubules and MAPs. Advances in Protein Chemistry 71: 257–298.

Asai DJ and Wilkes DE (2004) The dynein heavy chain family. Journal of Eukaryotic Microbiology 51: 23–29.

Ayaz P, Ye X, Huddleston P, Brautigam CA and Rice LM (2012) A TOG:αβ‐tubulin complex structure reveals conformation‐based mechanisms for a microtubule polymerase. Science 337: 857–860.

Aylett CH, Löwe J and Amos LA (2011) New insights into the mechanisms of cytomotive actin and tubulin filaments. International Review of Cell and Molecular Biology 292: 1–71.

Baas PW, Vidya Nadar C and Myers KA (2006) Axonal transport of microtubules: the long and short of it. Traffic 7: 490–498.

Brown A (2003) Axonal transport of membranous and nonmembranous cargoes: za unified perspective. Journal of Cell Biology 160: 817–821.

Brust‐Mascher I and Scholey JM (2011) Mitotic motors and chromosome segregation: the mechanism of anaphase B. Biochemical Society Transactions 39: 1149–1153.

Burbank KS and Mitchison TJ (2006) Microtubule dynamic instability. Current Biology 16: R516–R517.

Cassimeris L and Spittle C (2001) Regulation of microtubule‐associated proteins. International Review of Cytology 210: 163–226.

Chauvin S and Sobel A (2014) Neuronal stathmins: a family of phosphoproteins cooperating for neuronal development, plasticity and regeneration. Progress in Neurobiology 126: 1–18.

Chen J, Kanai Y, Cowan NJ and Hirokawa N (1992) Projection domains of MAP2 and tau determine spacings between microtubules in dendrites and axons. Nature 360: 674–677.

Cleveland DW, Lopata MA, Sherline P and Kirschner MW (1981) Unpolymerized tubulin modulates the level of tubulin mRNAs. Cell 25: 537–546.

Cross RA and McAinsh A (2014) Prime movers: the mechanochemistry of mitotic kinesins. Nature Reviews. Molecular Cell Biology 15: 257–271.

des Georges A, Katsuki M, Drummond DR, et al. (2008) Mal3, the Schizosaccharomyces pombe homolog of EB1, changes the microtubule lattice. Nature Structural & Molecular Biology 15: 1102–1108.

Diener DR, Yang P, Geimer S, et al. (2011) Sequential assembly of flagellar radial spokes. Cytoskeleton (Hoboken) 68: 389–400.

Duellberg C, Fourniol FJ, Maurer SP, Roostalu J and Surrey T (2013) End‐binding proteins and Ase1/PRC1 define local functionality of structurally distinct parts of the microtubule cytoskeleton. Trends in Cell Biology 23: 54–63.

Dutcher SK (2003) Elucidation of basal body and centriole functions in Chlamydomonas reinhardtii. Traffic 4: 443–451.

Gibbons IR (1996) The role of dynein in microtubule‐based motility. Cell Structure and Function 21: 331–342.

Gigant B, Cormier A, Dorléans A, Ravelli RB and Knossow M (2009) Microtubule‐destabilizing agents: structural and mechanistic insights from the interaction of colchicine and vinblastine with tubulin. Topics in Current Chemistry 286: 259–278.

Gustke N, Trinczek B, Biernat J, Mandelkow EM and Mandelkow E (1994) Domains of tau protein and interactions with microtubules. Biochemistry 33: 9511–9522.

Hinchcliffe EH (2014) Centrosomes and the art of mitotic spindle maintenance. International Review of Cell and Molecular Biology 313: 179–217.

Höög JL, Huisman SM, Sebö‐Lemke Z, et al. (2011) Electron tomography reveals a flared morphology on growing microtubule ends. Journal of Cell Science 124: 693–698.

Howard J and Hyman AA (2007) Microtubule polymerases and depolymerases. Current Opinion in Cell Biology 19: 31–35.

Iqbal K, Liu F, Gong CX and Grundke‐Iqbal I (2010) Tau in Alzheimer disease and related tauopathies. Current Alzheimer Research 7: 656–664.

Jiang K and Akhmanova A (2011) Microtubule tip‐interacting proteins: a view from both ends. Current Opinion in Cell Biology 23: 94–101.

Kalisman N, Schröder GF and Levitt M (2013) The crystal structures of the eukaryotic chaperonin CCT reveal its functional partitioning. Structure 21: 540–549.

Kar S, Fan J, Smith MJ, Goedert M and Amos LA (2003) Repeat motifs of tau bind to the insides of microtubules in the absence of taxol. EMBO Journal 22: 70–78.

Kinoshita K, Habermann B and Hyman AA (2002) XMAP215: a key component of the dynamic microtubule cytoskeleton. Trends in Cell Biology 12: 267–273.

Kollman JM, Merdes A, Mourey L and Agard DA (2011) Microtubule nucleation by γ‐tubulin complexes. Nature Reviews. Molecular Cell Biology 12: 709–721.

Kull FJ and Endow SA (2013) Force generation by kinesin and myosin cytoskeletal motor proteins. Journal of Cell Science 126: 9–19.

Kumar P and Wittmann T (2012) +TIPs: SxIPping along microtubule ends. Trends in Cell Biology 22: 418–428.

Lacroix B, van Dijk J, Gold ND, et al. (2010) Tubulin polyglutamylation stimulates spastin‐mediated microtubule severing. JCB 189: 945–954.

Li S, Fernandez JJ, Marshall WF and Agard DA (2012) Three‐dimensional structure of basal body triplet revealed by electron cryo‐tomography. EMBO Journal 31: 552–562.

Löwe J, Li H, Downing KH and Nogales E (2001) Refined structure of alpha beta‐tubulin at 3.5 A resolution. Journal of Molecular Biology 313: 1045–1057.

Mandelkow EM and Mandelkow E (1979) Junctions between microtubule walls. Journal of Molecular Biology 129: 135–148.

Magnani E, Fan J, Gasparini L, et al. (2007) Interaction of tau protein with the dynactin complex. EMBO Journal 26: 4546–4554.

McIntosh JR, Morphew MK, Grissom PM, Gilbert SP and Hoenger A (2009) Lattice structure of cytoplasmic microtubules in a cultured mammalian cell. Journal of Molecular Biology 394: 177–182.

Miller HP and Wilson L (2010) Preparation of microtubule protein and purified tubulin from bovine brain by cycles of assembly and disassembly and phosphocellulose chromatography. Methods in Cell Biology 95: 3–15.

Mitchison TJ (2005) Mechanism and function of poleward flux in Xenopus extract meiotic spindles. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 360: 623–629.

Morrison EE (2007) Action and interactions at microtubule ends. Cellular and Molecular Life Sciences 64: 307–317.

Nicastro D, Fu X, Heuser T, et al. (2011) Cryo‐electron tomography reveals conserved features of doublet microtubules in flagella. Proceedings of the National Academy of Sciences of the United States of America 108: E845–E853.

Oda T, Yanagisawa H, Kamiya R and Kikkawa M (2014) A molecular ruler determines the repeat length in eukaryotic cilia and flagella. Science 346: 857–860.

Pecqueur L, Duellberg C, Dreier B, et al. (2012) A designed ankyrin repeat protein selected to bind to tubulin caps the microtubule plus end. Proceedings of the National Academy of Sciences of the United States of America 109: 12011–12016.

Pigino G, Maheshwari A, Bui KH, et al. (2012) Comparative structural analysis of eukaryotic flagella and cilia from Chlamydomonas, Tetrahymena, and sea urchins. Journal of Structural Biology 178: 199–206.

Pigino G, Geimer S, Lanzavecchia S, et al. (2009) Electron‐tomographic analysis of intraflagellar transport particle trains in situ. Journal of Cell Biology 187: 135–148.

Prota AE, Bargsten K, Diaz JF, et al. (2014) A new tubulin‐binding site and pharmacophore for microtubule‐destabilizing anticancer drugs. Proceedings of the National Academy of Sciences of the United States of America 111: 13817–13821.

Ravelli RB, Gigant B, Curmi PA, et al. (2004) Insight into tubulin regulation from a complex with colchicine and a stathmin‐like domain. Nature 428: 198–202.

Sharp DJ and Ross JL (2012) Microtubule‐severing enzymes at the cutting edge. Journal of Cell Science 125: 2561–2569.

Slep KC (2010) Structural and mechanistic insights into microtubule end‐binding proteins. Current Opinion in Cell Biology 22: 88–95.

Snyder JP, Nettles JH, Cornett B, Downing KH and Nogales E (2001) The binding conformation of Taxol in beta‐tubulin: a model based on electron crystallographic density. Proceedings of the National Academy of Sciences of the United States of America 98: 5312–5316.

Song Y and Brady ST (2015) Post‐translational modifications of tubulin: pathways to functional diversity of microtubules. Trends in Cell Biology 25: 125–136.

Szolajska E and Chroboczek J (2011) Faithful chaperones. Cellular and Molecular Life Sciences 68: 3307–3322.

Szyk A, Deaconescu AM, Spector J, et al. (2014) Molecular basis for age‐dependent microtubule acetylation by tubulin acetyltransferase. Cell 157: 1405–1415.

Takemura R, Okabe S, Umeyama T, et al. (1992) Increased microtubule stability and alpha tubulin acetylation in cells transfected with microtubule‐associated proteins MAP1B, MAP2 or tau. Journal of Cell Science 103: 953–964.

Varma D and Salmon ED (2012) The KMN protein network ‐ chief conductors of the kinetochore orchestra. Journal of Cell Science 125: 5927–5936.

van der Vaart B, Akhmanova A and Straube A (2009) Regulation of microtubule dynamic instability. Biochemical Society Transactions 37: 1007–1013.

Vitre B, Coquelle FM, Heichette C, et al. (2008) EB1 regulates microtubule dynamics and tubulin sheet closure in vitro. Nature Cell Biology 10: 415–421.

Vulevic B and Correia JJ (1997) Thermodynamic and structural analysis of microtubule assembly: the role of GTP hydrolysis. Biophysical Journal 72: 1357–1375.

Further Reading

Amos LA (2011) What tubulin drugs tell us about microtubule structure and dynamics. Seminars in Cell & Developmental Biology 22: 916–926.

Dumont S, Salmon ED and Mitchison TJ (2012) Deformations within moving kinetochores reveal different sites of active and passive force generation. Science 337: 355–358.

Erickson HP and Stoffler D (1996) Protofilaments and rings, two conformations of the tubulin family conserved from bacterial FtsZ to alpha/beta and gamma tubulin. Journal of Cell Biology 135: 5–8.

Gardner MK, Zanic M and Howard J (2013) Microtubule catastrophe and rescue. Current Opinion in Cell Biology 25: 14–22.

Guizetti J and Gerlich DW (2010) Cytokinetic abscission in animal cells. Seminars in Cell & Developmental Biology 21: 909–916.

Roll‐Mecak A (2015) Intrinsically disordered tubulin tails: complex tuners of microtubule functions? Seminars in Cell & Developmental Biology 37C: 11–19.

Scholey JM (2008) Intraflagellar transport motors in cilia: moving along the cell's antenna. Journal of Cell Biology 180: 23–29.

Schuyler SC and Pellman D (2001) Microtubule ‘plus‐end‐tracking proteins’: the end is just the beginning. Cell 105: 421–424.

Sirajuddin M, Rice LM and Vale RD (2014) Regulation of microtubule motors by tubulin isotypes and post‐translational modifications. Nature Cell Biology 16: 335–344.

Wittmann T, Hyman A and Desai A (2001) The spindle: a dynamic assembly of microtubule motors. Nature Cell Biology 3: E28–E34.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Amos, Linda A(Jul 2015) Tubulin and Microtubules. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000676.pub3]