Structure of a Microtubule
Microtubules Forming the Mitotic Spindle in a Dividing Human Cell
Dynamic Instability in Microtubules
As polar filaments, with minus ends typically anchored in a centrosome or other MTOC, microtubules grow or shrink from their plus ends. Any individual microtubule may be either in a state of slow polymerization (growth) or fast depolymerization (shrinkage) at any given time. Microtubules may switch between these two states rapidly. This cyclic switching between growth and shrinkage is called dynamic instability.The factor that triggers switching between states in dynamic instability is the binding of guanosine-5′-triphosphate (GTP), which is an energy source for metabolic reactions, to tubulin subunits, and the subsequent hydrolysis of GTP to GDP. When GTP is bound to tubulin, the affinity of tubulin for the microtubule increases, so tubulin is more likely to bind to the microtubule than to depolymerize. After polymerization, GTP bound to the tubulin is hydrolyzed to guanosine diphosphate (GDP), which is a nucleoside diphosphate. As a result, the affinity of tubulin to the microtubule is weakened, and the subunit is more likely to depolymerize. However, if subunits bound to GTP polymerize rapidly, the rate of polymerization outstrips the rate of hydrolysis, and a "GTP cap" of subunits with GTP bound to them builds up. Microtubule growth continues as long as the rate of addition of these subunits is faster than the rate of hydrolysis. When the rate of addition slows, the hydrolysis of GTP to GDP catches up, until the subunits at the plus end of the microtubule are bound to GDP. At this point, the binding affinity drops, and the microtubule begins to depolymerize. As depolymerization continues, the protofilaments of the microtubule fray apart, depolymerization becomes rapid, and the microtubule disassembles. Dynamic instability gives the microtubule cytoskeleton the ability to reorganize quickly. This is especially important in the events of mitosis. It also means that the typical lifetime of a microtubule in a cell is only several minutes. In circumstances where the cell requires more stable microtubule structures, additional microtubule-associated proteins (MAPs) bind to the microtubules, which stabilizes them against depolymerization. Microtubules in the axons (extensions from the neuronal cell body that transmit the signal to receiving cells) and dendrites (extensions from the neuronal cell body that receive input from other cells) of nerve cells are examples of these stabilized microtubule structures.
Kinesins and Dyneins
The filaments of the cytoskeleton can provide structure and support, but in order to transport cellular materials or generate motion, cells rely on motor proteins. A motor protein is a protein, such as dynein or kinesin, that uses the energy released by the hydrolysis of ATP to move along a cytoskeletal filament. Microtubules associate with two families of motor proteins, the kinesins and the dyneins, that can move materials using the microtubules as tracks. A kinesin is a two-headed ATPase motor that moves materials from the minus end of microtubules toward the plus end. Kinesins move in a stepping fashion from one tubulin subunit to the next, maintaining an association with the filament for 100 steps or more. This long association is because of the conformational changes that occur when kinesins bind ATP. A kinesin head bound to tubulin increases its affinity and locks in place upon binding to ATP. The conformational change also positions the second head near the next tubulin subunit on the filament. When the first head hydrolyzes ATP and releases, the second one is ready to attach, this action also deters the motor protein from moving backwards.
Because they move from the minus to the plus ends of microtubules, kinesins can transport cytosolic cargo, such as potassium or sodium ions, from the center of the cell to the periphery. The endoplasmic reticulum has attachments to the opposite and of kinesin motors and acquires its extended, tubular structure by being pulled and stretched away from the nucleus by kinesins traveling along microtubules.A dynein is a motor protein that moves from the plus end to the minus end of microtubules. Dyneins are much larger ATPase motors than kinesins, with molecular weights of about 1.2 MDa compared to 120 kDa for kinesins. Since the plus ends of microtubules are generally located at the edges of cell, dyneins are used to move materials from the edges of the cell toward the center. They transport a wide variety of cargoes, including endocytotic vesicles, lysosomes, peroxisomes, and viruses. They are also used to position discrete organelles, such as mitochondria, and extended ones, such as the Golgi apparatus, whose membrane chambers are pulled close to the nucleus by the action of dyneins. Dyneins may also exert tension on the nucleus and the centrosome, helping to center them.