Dynamics of the filament The
cytoskeleton is a highly dynamic part of a cell and cytoskeletal filaments constantly grow and shrink through addition and removal of subunits. Directed crawling motion of cells such as
macrophages relies on directed growth of actin filaments at the cell front (
leading edge).
Microfilaments The two ends of an actin filament differ in their dynamics of subunit addition and removal. They are thus referred to as the
plus end (with faster dynamics, also called barbed end) and the
minus end (with slower dynamics, also called pointed end). This difference results from the fact that subunit addition at the minus end requires a
conformational change of the subunits. Note that each subunit is structurally polar and has to attach to the filament in a particular orientation. As a consequence, the actin filaments are also structurally polar. Elongating the actin filament occurs when free-actin (G-actin) bound to ATP associates with the filament. Under physiological conditions, it is easier for G-actin to associate at the positive end of the filament, and harder at the negative end. However, it is possible to elongate the filament at either end. Association of G-actin into F-actin is regulated by the critical concentration outlined below. Actin polymerization can further be regulated by
profilin and
cofilin. Dynamic instability occurs when the microtubule assembles and disassembles at one end only, while treadmilling occurs when one end polymerizes while the other end disassembles.
Critical concentration The critical concentration is the concentration of either G-actin (actin) or the alpha,beta- tubulin complex (microtubules) at which the end will remain in an equilibrium state with no net growth or shrinkage. Critical concentration differs from the plus (CC+) and the minus end (CC−), and under normal physiological conditions, the critical concentration is lower at the plus end than the minus end. Examples of how the cytosolic concentration relates to the critical concentration and polymerization are as follows: • A cytosolic concentration of subunits above both the CC+ and CC− ends results in subunit addition at both ends • A cytosolic concentration of subunits below both the CC+ and CC− ends results in subunit removal at both ends Note that the cytosolic concentration of the monomer subunit between the CC+ and CC− ends is what is defined as treadmilling in which there is growth at the plus end, and shrinking on the minus end. The cell attempts to maintain a subunit concentration between the dissociation constants at the plus and minus ends of the polymer.
Microtubule treadmilling Microtubules formed from pure tubulin undergo subunit uptake and loss at ends by both random exchange diffusion, and by a directional (treadmilling) element. Treadmilling is inefficient, and for microtubules at steady state: the Wegner s-value1 (the reciprocal of the number of molecular events required for the net uptake of a subunit) is equal to 0.0005-0.001; i.e., it requires >1000 events. Microtubule treadmilling with pure tubulin also occurs with growing microtubules and is enhanced by proteins that bind to ends11. Rapid treadmilling occurs in cells.
FtsZ treadmilling The bacterial tubulin homolog
FtsZ is one of the best documented treadmilling polymers. FtsZ assembles into protofilaments that are one subunit thick, which can further associate into small patches of parallel protofilaments. Single filaments and/or patches have been demonstrated to treadmill in vitro and inside bacterial cells. A Monte Carlo model of FtsZ treadmilling has been designed, based on a conformational change of subunits upon polymerization and GTP hydrolysis. == References ==