Question

Describe the G-protein-like regulation of MT and MF

Apply the concepts of critical concentration & dynamic instability to understanding MT assembly and disassembly

Answer 1

Dynamic Instability is the ability of Microtubule (MT) to assemble and disassembly from the same position which are the ends of MT and hence it can switch between polymerisation and depolymerisation (shrinking and growing).

Crirical Concentration is the equilibrium concentration of MT, ??-tubulin dimers such that there is no longer any net assembly or disassembly at the end of the microtubule. When the dimer concentration is more than critical the MT will grow, while it will decrease when the concentration is low.

In the process of polymerization, the ??-tubulin dimers are in the GTP bound state. The GTP bound to ?-tubulin is quite stable and it plays a structural role in this GTP bound state of the alpha subunit. Whereas GTP bound to ?-tubulin may or may not get hydrolyzed to GDP after assembly. The assembly properties of GDP-tubulin are quite different from those of GTP tubulin, as GDP tubulin is more vulnerable to shrinkage. A GDP bound tubulin subunit at the tip of a MT will most likely fall, while a GDP bound tubulin in the middle of a MT cannot spontaneously break away from the polymer. Since tubulin adds to the end of the microtubule in the GTP bound state, a cap of GTP bound tubulin is exists at the tip of the MT, which protects it from disassembly. When hydrolysis gets to the tip of the MT, it begins a rapid depolymerization and shrinkage. This switch from polymerisation to depolymerisation is called a catastrophe. GTP bound tubulin can begin to add to the tip of the microtubule again, giving the MT a new cap and protecting the MT from shrinking. In this way MT is reguated like a G-protein.

Microfilaments or MF are polymers of actin subunits globular actin also called G-actin, which being part of the fiberous filament are referred to as filamentous actin, or F-actin. Just like MT, actin filaments are polarized i.e they have two specific ends. The pointed end is commonly referred to as the minus ? end and the barbed end is referred to as the plus + end.

Actin polymerization and nucleation, begins with the self assembly of 3 G actin monomers to form a trimer. ATP bound actin then itself binds the barbed end, and the ATP is then hydrolyzed. This autocatalyzed event decreases the affinity and hence the binding strength between neighboring subunits, and thus generally destabilizes the filament. this is followed by ADP-actin dissociation slowly from the pointed end, a process catalyzed by the actin-binding protein, cofilin. ADP bound cofilin severs ADP-rich regions nearest the (?)ends. After it's release, the free actin monomer slowly dissociates from ADP, which then quickly binds to the free ATP diffused in the cytosol, subsequently forming the ATP actin monomeric units needed for further barbed-end filament elongation. Thus it is also carefully controlled and regulated like G protein.

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