Microtubule
Encyclopedia
Cytoskeleton
The 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...
. These rope-like polymers of tubulin
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...
can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm
Nanometre
A nanometre is a unit of length in the metric system, equal to one billionth of a metre. The name combines the SI prefix nano- with the parent unit name metre .The nanometre is often used to express dimensions on the atomic scale: the diameter...
. Microtubules are important for maintaining cell structure, providing platforms for intracellular transport, forming the spindle 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...
, as well as other cellular processes. There are many proteins that bind to the microtubule, including motor proteins such as kinesin
Kinesin
A 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...
and dynein
Dynein
Dynein 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...
, severing proteins like 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...
, and other proteins important for regulating microtubule dynamics.
Structure
Microtubules are polymers of α- and β-tubulinTubulin
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...
dimers
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
. The tubulin dimers polymerize end to end in protofilaments. Typically 13 protofilaments associate laterally to form the microtubule, although microtubules containing 14 protofilaments have been seen in vitro.The protofilaments arrange themselves in an imperfect helix
Helix
A helix is a type of smooth space curve, i.e. a curve in three-dimensional space. It has the property that the tangent line at any point makes a constant angle with a fixed line called the axis. Examples of helixes are coil springs and the handrails of spiral staircases. A "filled-in" helix – for...
with one turn of the helix containing 13 tubulin dimers each from a different protofilament. The image above illustrates a small section of microtubule, a few αβ dimers in length.
Another important feature of microtubule structure is polarity. Tubulin polymerizes end to end with the α subunit of one tubulin dimer contacting the β subunit of the next. Therefore, in a protofilament, one end will have the α subunit exposed while the other end will have the β subunit exposed. These ends are designated the (−) and (+) ends, respectively. The protofilaments bundle parallel to one another, so in a microtubule, there is one end, the (+) end, with only β subunits exposed while the other end, the (−) end, only has α subunits exposed. The (-) end is capped so elongation of the microtubule occurs from the (+) direction.
Organization within cells
Microtubules are nucleated and organized by the microtubule organizing centerMicrotubule organizing center
The microtubule-organizing center is a structure found in eukaryotic cells from which microtubules emerge. MTOCs have two main functions: the organization of eukaryotic flagella and cilia and the organization of the mitotic and meiotic spindle apparatus, which separate the chromosomes during cell...
s (MTOCs), such as centriole
Centriole
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 basal bodies
Basal body
A basal body is an organelle formed from a centriole, and a short cylindrical array of microtubules. It is found at the base of a eukaryotic undulipodium and serves as a nucleation site for the growth of the axoneme microtubules...
. Microtubules are part of a structural network (the cytoskeleton
Cytoskeleton
The 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...
) within the cell's cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
, but, in addition to structural support, microtubules take part in many other processes. They are capable of growing and shrinking in order to generate force, and there are also motor proteins that allow organelles and other cellular factors to move along the microtubule. A notable structure involving microtubules is 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...
used by eukaryotic
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...
cells to segregate their chromosomes correctly during cell division. Microtubules are also part of the cilia and flagella
Flagellum
A flagellum is a tail-like projection that protrudes from the cell body of certain prokaryotic and eukaryotic cells, and plays the dual role of locomotion and sense organ, being sensitive to chemicals and temperatures outside the cell. There are some notable differences between prokaryotic and...
of eukaryotic cell
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 (prokaryote
Prokaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...
flagella are entirely different).
The process of mitosis is facilitated by a subgroup of microtubules known as astral microtubules
Astral microtubules
Astral microtubules are a subpopulation of microtubules, which only exist during and immediately before mitosis. They are defined as any microtubule originating from the centrosome which does not connect to a kinetochore. Astral microtubules develop in the actin skeleton and interact with the cell...
, defined as a microtubule originating from the centrosome that does not connect to a kinetochore
Kinetochore
The kinetochore is the protein structure on chromatids where the spindle fibers attach during cell division to pull sister chromatids apart....
. Astral microtubules develop in the actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
skeleton and interact with the cell cortex to aid in spindle orientation. They are organized into radial arrays around the centrosomes. The turn-over rate of this population of microtubules is higher than any other population. Astral microtubules function in concert with specialized dynein
Dynein
Dynein 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...
motors, which are oriented with the light chain portion attached to the cell membrane and the dynamic portion attached to the microtubule. This allows for dynein contraction to pull the centrosome toward the cell membrane, thus assisting in cytokinesis
Cytokinesis
Cytokinesis is the process in which the cytoplasm of a single eukaryotic cell is divided to form two daughter cells. It usually initiates during the late stages of mitosis, and sometimes meiosis, splitting a binucleate cell in two, to ensure that chromosome number is maintained from one generation...
.
Astral microtubules are not required for the progression of mitosis, but they are required to ensure the fidelity of the process; they are required for the correct positioning and orientation of the mitotic spindle apparatus. They are also involved in determination of cell division site based on the geometry and polarity of the cells.
The maintenance of astral microtubules is dependent on the integrity of centrosome. It is also dependent on several microtubule-associated proteins such as EB1 and Adenomatous Polyposis Coli (APC).
Nucleation and growth
Polymerization of microtubules is nucleated in a microtubule organizing center. Contained within the MTOC is another type of tubulin, γ-tubulin, which is distinct from the α and β subunits, which compose the microtubules themselves. The γ-tubulin combines with several other associated proteins to form a circular structure known as the "γ-tubulin ring complex." This complex acts as a scaffold for α/β tubulin dimers to begin polymerization; it acts as a cap of the (−) end while microtubule growth continues away from the MTOC in the (+) direction.Dynamic instability
Dynamic instability refers to the coexistence of assembly and disassembly at the (+) end of a microtubule. The microtubule can switch between the growing and shrinking phases dynamically at this region. During polymerization, both the α- and β-subunits of the tubulin dimer are bound to a molecule of GTPGuanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...
. While the GTP bound to α-tubulin is stable, the GTP bound to β-tubulin may be hydrolyzed
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...
to GDP shortly after assembly. The kinetics of GDP-tubulin are different from those of GTP-tubulin; GDP-tubulin is prone to depolymerization. A GDP-bound tubulin subunit at the tip of a microtubule will fall off, though a GDP-bound tubulin in the middle of a microtubule cannot spontaneously pop out. Since tubulin adds onto the end of the microtubule only in the GTP-bound state, there is a cap of GTP-bound tubulin at the tip of the microtubule, protecting it from disassembly. When hydrolysis catches up to the tip of the microtubule, it begins a rapid depolymerization and shrinkage. This switch from growth to shrinking is called a catastrophe. GTP-bound tubulin can begin adding to the tip of the microtubule again, providing a new cap and protecting the microtubule from shrinking. This is referred to as "rescue."
Microtubule-associated protein
In cell biology, microtubule-associated proteins are proteins that interact with the microtubules of the cellular cytoskeleton.-Function:...
s (MAPs
Microtubule-associated protein
In cell biology, microtubule-associated proteins are proteins that interact with the microtubules of the cellular cytoskeleton.-Function:...
) are present.
Chemical effects on microtubule dynamics
Microtubule dynamics can also be altered by drugs.
- For example, the cancer fighting taxaneTaxaneThe taxanes are diterpenes produced by the plants of the genus Taxus . As their name suggests, they were first derived from natural sources, but some have been synthesized artificially. Taxanes include paclitaxel and docetaxel . Paclitaxel was originally derived from the Pacific yew tree.Taxanes...
class drugs paclitaxelPaclitaxelPaclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...
[taxol] and docetaxel block dynamic instability by stabilizing GDP-bound tubulin in the microtubule. Thus, even when hydrolysis of GTP reaches the tip of the microtubule, there is no depolymerization and the microtubule does not shrink back.
- The EpothiloneEpothiloneThe epothilones are a new class of cancer drugs. Like taxanes, they prevent cancer cells from dividing by interfering with tubulin, but in early trials epithilones have better efficacy and milder adverse effects than taxanes....
s, eg. IxabepiloneIxabepiloneIxabepilone is an epothilone B analog developed by Bristol-Myers Squibb as a cancer drug.It is produced by Sorangium cellulosum.-Pharmacology:It acts to stabilize microtubules....
, work in a similar way to the taxanes.
- NocodazoleNocodazoleNocodazole is an anti-neoplastic agent which exerts its effect in cells by interfering with the polymerization of microtubules. Microtubules are one type of fibre which constitutes the cytoskeleton, and the dynamic microtubule network has several important roles in the cell, including vesicular...
, vincristineVincristineVincristine , 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...
, and ColchicineColchicineColchicine is a medication used for gout. It is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum...
have the opposite effect, blocking the polymerization of tubulin into microtubules.
- EribulinEribulinEribulin is an anticancer drug marketed by Eisai Co. under the trade name Halaven. Eribulin mesylate was approved by the U.S. Food and Drug Administration on November 15, 2010, to treat patients with metastatic breast cancer who have received at least two prior chemotherapy regimens for late-stage...
binds to the (+) growing end of the microtubules.
Motor proteins
In addition to movement generated by the dynamic instability of the microtubule itself, the fibers are substrates along which motor proteins can move. The major microtubule motor proteins are kinesinKinesin
A 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...
, which moves toward the (+) end of the microtubule, and dynein
Dynein
Dynein 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...
, which moves toward the (−) end.
Postulated role in consciousness
In their controversial Orch-OROrch-OR
Orch-OR is a theory of consciousness, which is the joint work of theoretical physicist Sir Roger Penrose and anesthesiologist Stuart Hameroff. Mainstream theories assume that consciousness emerges from the brain, and focus particularly on complex computation at synapses that allow communication...
theory of consciousness
Consciousness
Consciousness is a term that refers to the relationship between the mind and the world with which it interacts. It has been defined as: subjectivity, awareness, the ability to experience or to feel, wakefulness, having a sense of selfhood, and the executive control system of the mind...
, Roger Penrose
Roger Penrose
Sir Roger Penrose OM FRS is an English mathematical physicist and Emeritus Rouse Ball Professor of Mathematics at the Mathematical Institute, University of Oxford and Emeritus Fellow of Wadham College...
and Stuart Hameroff
Stuart Hameroff
Stuart Hameroff is an anesthesiologist and professor at the University of Arizona known for his scientific studies of consciousness.-Career:...
postulate that microtubules in neurons conduct quantum
Quantum mechanics
Quantum mechanics, also known as quantum physics or quantum theory, is a branch of physics providing a mathematical description of much of the dual particle-like and wave-like behavior and interactions of energy and matter. It departs from classical mechanics primarily at the atomic and subatomic...
-level manipulations of matter, which produces consciousness, based partially on some observations of Gamma Synchrony that indicate that information may propagate through the brain much faster than a chemically mediated neural network
Neural network
The term neural network was traditionally used to refer to a network or circuit of biological neurons. The modern usage of the term often refers to artificial neural networks, which are composed of artificial neurons or nodes...
would physically permit. Max Tegmark
Max Tegmark
Max Tegmark is a Swedish-American cosmologist. Tegmark is a professor at the Massachusetts Institute of Technology and belongs to the scientific directorate of the Foundational Questions Institute.-Early life:...
disputes the relevance of these observations, and the matter remains open to debate. David Chalmers argues that quantum theories of consciousness suffer from the same weakness as more conventional theories. Just as he argues that there is no particular reason why particular macroscopic physical features in the brain should give rise to consciousness, he also thinks that there is no particular reason why a particular quantum feature, such as the EM field in the brain, should give rise to consciousness either. While at least one researcher
Michael Persinger
Michael A. Persinger is a cognitive neuroscience researcher and university professor with over 200 peer-reviewed publications. He has worked at Laurentian University, located in Sudbury, Ontario, since 1971.-Early life:...
claims otherwise, Jeffrey Gray
Jeffrey Alan Gray
Jeffrey Alan Gray was a British psychologist. He was born in the East End of London. His father was a tailor, but died when Jeffrey was only seven. His mother, who ran a haberdashery, brought him up alone....
states in his book Consciousness: Creeping up on the Hard Problem, that tests looking for the influence of electromagnetic fields on brain function have been universally negative in their result.