Tubulin
Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and β-tubulin. These subunits are slightly acidic with an isoelectric point between 5.2 and 5.8.[1]
Tubulin was long thought to be specific to eukaryotes. Recently, however, the prokaryotic cell division protein FtsZ was shown to be evolutionarily related to tubulin.[2]
α-tubulin and β-tubulin
To form microtubules, the dimers of α- and β-tubulin bind to GTP and assemble onto the (+) ends of microtubules while in the GTP-bound state.[3] After the dimer is incorporated into the microtubule, the molecule of GTP bound to the β-tubulin subunit eventually hydrolyses into GDP through inter-dimer contacts along the microtubule protofilament.[4]. Whether the β-tubulin member of the tubulin dimer is bound to GTP or GDP influences the stability of the dimer in the microtubule.
Dimers bound to GTP tend to assemble into microtubules, while dimers bound to GDP tend to fall apart; thus, this GTP cycle is essential for the dynamic instability of the microtubule.
Class III β-tubulin is a microtubule element expressed exclusively in neurons, and is a popular identifier specific for neurons in nervous tissue.
Katanin is a protein complex that severs microtubules at β-tubulin subunits, and is necessary for rapid microtubule transport in neurons and in higher plants.[5]
Human α- and β-tubulin subtypes include:[6]
γ-tubulin
γ-tubulin, another member of the tubulin family, is important in the nucleation and polar orientation of microtubules. It is found primarily in centrosomes and spindle pole bodies, since these are the areas of most abundant microtubule nucleation. In these organelles, several γ-tubulin and other protein molecules are found in complexes known as γ-tubulin ring complexes (γ-TuRCs), which chemically mimic the (+) end of a microtubule and thus allow microtubules to bind. γ-tubulin also has been isolated as a dimer and as a part of a γ-tubulin small complex (γTuSC), intermediate in size between the dimer and the γTuRC. γ-tubulin is the best understood mechanism of microtubule nucleation, but certain studies have indicated that certain cells may be able to adapt to its absence, as indicated by mutation and RNAi studies that have inhibited its correct expression.
Human γ-tubulin subtypes include:[6]
δ and ε tubulin
Delta (δ) and epsilon (ε) tubulin have been found to localize at centrioles and may play a role in forming the mitotic spindle during mitosis, though neither is as well-studied as the α- and β- forms.
Human δ- and ε-tubulin subtypes include:[6]
Pharmacology
Tubulins are targets for anticancer drugs like Taxol and the "Vinca alkaloid" drugs such as vinblastine and vincristine. The anti-gout agent colchicine binds to tubulin and inhibits microtubule formation, arresting neutrophil motility and decreasing inflammation. The anti-fungal drug Griseofulvin targets mictotubule formation and has applications in cancer treatment.
Preparation
Tubulin Preparation from Protocolmonkey
See also
References
- ^ Williams RC Jr, Shah C, Sackett D (1999). "Separation of tubulin isoforms by isoelectric focusing in immobilized pH gradient gels". Anal Biochem. 275 (2): 265–7. doi:10.1006/abio.1999.4326. PMID 10552916.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Nogales E, Downing KH, Amos LA, Löwe J (1998). "Tubulin and FtsZ form a distinct family of GTPases". Nat Struct Biol. 5 (6): 451–8. doi:10.1038/nsb0698-451. PMID 9628483.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Heald R, Nogales E (2002). "Microtubule dynamics". J Cell Sci. 115 (Pt 1): 3–4. PMID 11801717.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Howard J, Hyman AA (2003). "Dynamics and mechanics of the microtubule plus end". Nature. 422 (6933): 753–8. doi:10.1038/nature01600. PMID 12700769.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ McNally FJ, Vale RD (1993). "Identification of katanin, an ATPase that severs and disassembles stable microtubules". Cell. 75 (3): 419–29. PMID 8221885.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ a b c Dutcher SK; Vale, RD (2001). "The tubulin fraternity: alpha to eta". Curr Opin Cell Biol. 13 (1): 49–54. PMID 8221885.
{{cite journal}}: Unknown parameter|month=ignored (help)
External links
- Tubulin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- EC 3.6.5.6