Tubulin
Encyclopedia
Tubulin is one of several members of a small family of globular protein
s. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubule
s. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimer
s of α- and β-tubulin. These subunits are slightly acidic with an isoelectric point
between 5.2 and 5.8.
Tubulin was long thought to be specific to eukaryote
s. Recently, however, the prokaryotic cell division protein FtsZ
was shown to be related to 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. After the dimer is incorporated into the microtubule, the molecule of GTP bound to the β-tubulin subunit eventually hydrolyzes
into GDP through inter-dimer contacts along the microtubule protofilament. Whether the β-tubulin member of the tubulin dimer is bound to GTP or GDP influences the stability of the dimer in the microtubule. β-tubulin faces the plus end of the microtubule while α-tubulin faces the minus end. That is, the β (-) side of added dimers connect to the plus end whereas the α sides (+) point outwards and connect to incoming minus ends.
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 neuron
s, 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.
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:
s 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:
like Taxol, Tesetaxel
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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
s. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimer
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
s of α- and β-tubulin. These subunits are slightly acidic with an isoelectric point
Isoelectric point
The isoelectric point , sometimes abbreviated to IEP, is the pH at which a particular molecule or surface carries no net electrical charge....
between 5.2 and 5.8.
Tubulin was long thought to be specific to eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s. Recently, however, the prokaryotic cell division protein FtsZ
FtsZ
FtsZ is a protein encoded by the ftsZ gene that assembles into a ring at the future site of the septum of bacterial cell division. This is a prokaryotic homologue to the eukaryotic protein tubulin. FtsZ has been named after "Filamenting temperature-sensitive mutant Z". The hypothesis was that cell...
was shown to be related to tubulin.
To form microtubules, the dimers of α- and β-tubulin bind to GTP
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...
and assemble onto the (+) ends of microtubules while in the GTP-bound state. After the dimer is incorporated into the microtubule, the molecule of GTP bound to the β-tubulin subunit eventually hydrolyzes
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
into GDP through inter-dimer contacts along the microtubule protofilament. Whether the β-tubulin member of the tubulin dimer is bound to GTP or GDP influences the stability of the dimer in the microtubule. β-tubulin faces the plus end of the microtubule while α-tubulin faces the minus end. That is, the β (-) side of added dimers connect to the plus end whereas the α sides (+) point outwards and connect to incoming minus ends.
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.
α-Tubulin
Human α-tubulin subtypes include:- α-Tubulin
- TUBA1ATUBA1ATubulin alpha-1A chain is a protein that in humans is encoded by the TUBA1A gene.-Interactions:TUBA1A has been shown to interact with PAFAH1B1.-Further reading:...
- TUBA1BTUBA1BTubulin alpha-1B chain is a protein that in humans is encoded by the TUBA1B gene.-Further reading:...
- TUBA1CTUBA1CTubulin alpha-1C chain is a protein that in humans is encoded by the TUBA1C gene.-Further reading:...
- TUBA3C
- TUBA3D
- TUBA3E
- TUBA4ATUBA4ATubulin alpha-4A chain is a protein that in humans is encoded by the TUBA4A gene.-Interactions:TUBA4A has been shown to interact with NCOA6 and APC.-Further reading:...
- TUBA8TUBA8Tubulin alpha-8 chain is a protein that in humans is encoded by the TUBA8 gene.-Further reading:...
- TUBA1A
β-Tubulin
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s, and is a popular identifier specific for neurons in nervous tissue.
Katanin
Katanin
Katanin is a microtubule-severing AAA protein. It is named after the Japanese sword, katana. Katanin is a heterodimeric protein first discovered in sea urchins. It contains a 60 kDa ATPase subunit, which functions to sever microtubules. This subunit requires ATP and the presence of microtubules...
is a protein complex that severs microtubules at β-tubulin subunits, and is necessary for rapid microtubule transport in neurons and in higher plants.
- β-Tubulin
- TUBBTUBBTubulin beta chain is a protein that in humans is encoded by the TUBB gene.-Interactions:TUBB has been shown to interact with NCOA6 and SYT9.-Further reading:...
- TUBB1TUBB1Tubulin beta-1 chain is a protein that in humans is encoded by the TUBB1 gene.-Further reading:...
- TUBB2ATUBB2ATubulin beta-2A chain is a protein that in humans is encoded by the TUBB2A gene.-Further reading:...
- TUBB2B
- TUBB2CTUBB2CTubulin beta-2C chain is a protein that in humans is encoded by the TUBB2C gene.-Further reading:...
- TUBB3TUBB3Tubulin beta-3 chain is a protein that in humans is encoded by the TUBB3 gene.-Further reading:- External links :* **...
- TUBB4TUBB4Tubulin beta-4 chain is a protein that in humans is encoded by the TUBB4 gene.-Further reading:...
- TUBB4Q
- TUBB6
- TUBB
γ-Tubulin
γ-Tubulin, another member of the tubulin family, is important in the nucleationMicrotubule nucleation
Microtubules are filaments of the cytoskeleton. They typically form through the polymerization of α- and β-tubulin dimers elongating existing microtubules...
and polar orientation of microtubules. It is found primarily in centrosomes and spindle pole bodies
Spindle pole body
The spindle pole body is the microtubule organizing center in yeast cells, functionally equivalent to the centrosome. Unlike the centrosome the SPB does not contain centrioles. The SPB organises the microtubule cytoskeleton which plays many roles in the cell...
, 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
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
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
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
and RNAi
RNAI
RNAI is a non-coding RNA that is an antisense repressor of the replication of some E. coli plasmids, including ColE1. Plasmid replication is usually initiated by RNAII, which acts as a primer by binding to its template DNA. The complementary RNAI binds RNAII prohibiting it from its initiation role...
studies that have inhibited its correct expression.
Human γ-tubulin subtypes include:
- TUBG1Microtubule nucleationMicrotubules are filaments of the cytoskeleton. They typically form through the polymerization of α- and β-tubulin dimers elongating existing microtubules...
- TUBG2TUBG2Tubulin gamma-2 chain is a protein that in humans is encoded by the TUBG2 gene.-Further reading:...
- TUBGCP2TUBGCP2Gamma-tubulin complex component 2 is a protein that in humans is encoded by the TUBGCP2 gene.-Further reading:...
- TUBGCP3TUBGCP3Gamma-tubulin complex component 3 is a protein that in humans is encoded by the TUBGCP3 gene.-Further reading:...
- TUBGCP4
- TUBGCP5TUBGCP5Gamma-tubulin complex component 5 is a protein that in humans is encoded by the TUBGCP5 gene.-Further reading:...
- TUBGCP6TUBGCP6Gamma-tubulin complex component 6 is a protein that in humans is encoded by the TUBGCP6 gene.-Further reading:...
δ And ε tubulin
Delta (δ) and epsilon (ε) tubulin have been found to localize at centrioleCentriole
A Centriole is a barrel-shaped cell structure found in most animal eukaryotic cells, though it is absent in higher plants and most fungi. The walls of each centriole are usually composed of nine triplets of microtubules...
s and may play a role in forming the mitotic spindle
Mitotic spindle
In cell biology, the spindle fibers are the structure that separates the chromosomes into the daughter cells during cell division. It is part of the cytoskeleton in eukaryotic cells...
during mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
, though neither is as well-studied as the α- and β- forms.
Human δ- and ε-tubulin subtypes include:
- δ-tubulin
- TUBD1
- ε-tubulin
- TUBE1
Pharmacology
Tubulins are targets for anticancer drugsMedication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
like Taxol, Tesetaxel
Genta (company)
Genta Inc. is a biopharmaceutical company based in Berkeley Heights, New Jersey, United States, which develops products for the treatment of patients with cancer.Its products include:*Genasense...
and the "Vinca alkaloid" drugs such as vinblastine
Vinblastine
Vinblastine is an antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin's lymphoma, non-small cell lung cancer, breast cancer, head and neck cancer, and testicular cancer. It is also used to treat Langerhan cell histiocytosis....
and vincristine
Vincristine
Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to...
. The anti-gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
agent colchicine
Colchicine
Colchicine is a medication used for gout. It is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum...
binds to tubulin and inhibits microtubule formation, arresting neutrophil
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
motility and decreasing inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. The anti-fungal drug Griseofulvin
Griseofulvin
Griseofulvin is an antifungal drug that is administered orally. It is used both in animals and in humans, to treat fungal infections of the skin and nails...
targets mictotubule formation and has applications in cancer treatment.
See also
- MicrotubuleMicrotubuleMicrotubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
- CytoskeletonCytoskeletonThe cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
- Motor protein
- KinesinKinesinA kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule filaments, and are powered by the hydrolysis of ATP . The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cellular...
- DyneinDyneinDynein is a motor protein in cells which converts the chemical energy contained in ATP into the mechanical energy of movement. Dynein transports various cellular cargo by "walking" along cytoskeletal microtubules towards the minus-end of the microtubule, which is usually oriented towards the cell...
- FtsZFtsZFtsZ is a protein encoded by the ftsZ gene that assembles into a ring at the future site of the septum of bacterial cell division. This is a prokaryotic homologue to the eukaryotic protein tubulin. FtsZ has been named after "Filamenting temperature-sensitive mutant Z". The hypothesis was that cell...