Each actin molecule carries a tightly bound ATP molecule that is hydrolyzed to a tightly bound ADP molecule soon after its assembly into the polymer. Similarly, each tubulin molecule carries a tightly bound GTP that is converted to a tightly bound
GDP molecule soon after the molecule assembles into the polymer.
Hydrolysis of the bound nucleotide reduces the binding affnity of the subunit for neighboring subunits and makes it more likely to dissociate from each end of the flament (see Figure 16–44 for a possible mechanism). It is usually the           form that adds to the flament and the            form that leaves.
Considering events at the plus end only:
As before, the polymer will grow until C = Cc. For illustrative purposes, we can ignore kD and kToff since they are usually very small, so that polymer growth ceases when
This is a steady state and not a true equilibrium, because the ATP or GTP that is hydrolyzed must be replenished by a nucleotide exchange reaction of the free subunit (             ).
One consequence of the nucleotide hydrolysis that accompanies polymer formation is to change the critical concentration at the two ends of the polymer. Since kDoff and kT refer to different reactions, their ratio on kDoff/kTon need not be the same at both ends of the polymer, so that:
Thus, if both ends of a polymer are exposed, polymerization proceeds until the concentration of free monomer reaches a value that is above Cc for the plus end but below Cc for the minus end. At this steady state, subunits undergo a net assembly at the plus end and a net disassembly at the minus end at an identical rate. The polymer maintains a constant length, even though there is a net fux of subunits through the polymer, known as treadmilling.
Microtubules depolymerize about 100 times faster from an end containing GDP-tubulin than from one containing GTP-tubulin. A GTP cap favors growth, but if it is lost, then depolymerization ensues.
The rate of addition of subunits to a can be faster than the rate at which their bound nucleotide is hydrolyzed. Under such conditions, the end has a “cap” of subunits containing the nucleoside flament or a GTP cap on a microtubule.
DYNAMIC INSTABILITY and TREADMILLING are two behaviors observed in cytoskeletal polymers. Both are associated with nucleoside triphosphate hydrolysis. Dynamic instability is believed to predominate in microtubules, whereas treadmilling may predominate in actin flaments.
Individual microtubules can therefore alternate between a period of slow growth and a period of rapid disassembly, a phenomenon called dynamic instability.
Figure 16–14 Treadmilling of an actin soluble subunits are in T form ( filament, made possible by the ATP hydrolysis that follows subunit addition.
polymers are a mixture of T form ( (A) Explanation for the different critical concentrations (Cc) at the plus and minus at D minus a growing filament, and then undergo ends. Subunits with bound ATP (T-form nucleotide hydrolysis within the filament. As minus-end addition is slow— plus-end addition is fast— while the total length of the filament remains unchanged. This “steady-state tread-milling” requires a constant consumption of energy in the form of ATP hydrolysis.
The Functions of Actin Filaments Are Inhibited by Both Polymer-stabilizing and Polymer-destabilizing Chemicals