Polymerization Dynamics of Cytoskeletal Filaments

Polymerization dynamics is the description of the equilibrium between polymeric and monomeric states. The proteins of the cytoskeleton are able to polymerize and depolymerize through continuous cycles of addition or subtraction of monomer units, and the cytoskeleton is not a static entity.

Keywords: actin; tubulin; microtubule; intermediate filament proteins

Figure 1. A generalized scheme for the polymerization/depolymerization rates at the ends of microtubules and microfilaments. The fast-growing end refers to the barbed end in the case of microfilaments and the plus end for microtubules, whereas the slow growing end is the pointed end of microfilaments and the minus end of microtubules. Note that in both cases NTP subunits preferentially join the filament at the fast growing end and NDP subunits preferentially leave it at the slow growing end.
Figure 2. Polarity of cytoskeletal structures in various cell types. Microtubules in (a) mitotic spindle (antiparallel) and (b) axon (parallel); cell body to right. Microfilaments: (c) contractile ring in cytokinesis (antiparallel) and (d) microfilament bundles in microvillus (parallel); cell body to right.
Figure 3. Dynamic instability of microtubules. (a) GTP dimers (dark blue) cap both ends of a microtubule, making it stable as the off rate is low. (b) GDP dimers (light blue) are exposed at the minus end, making it very unstable because of the high off rate. As dimers (usually GTP dimers) may add to either end of a microtubule, both ends are likely to have GTP dimers. However, if the rate of GTP hydrolysis exceeds the rate of dimer addition even transiently, GDP dimers will be exposed and the filament will rapidly disassemble.
Figure 4. Treadmilling of microtubules and microfilaments. Subunit number 1 (shaded) adds to the end of a polymer as number 5 leaves (top). Some time later, subunit 0 adds and, although the filament has not necessarily changed length, subunit number 1 has moved relative to the polymer. Later still (bottom) subunit number –1 joins and subunit 4 leaves, causing subunit 1 to move relatively further down the polymer. The events at both ends of the filament are independent except that monomers leaving the pointed end will then be able to join the barbed end.
Figure 5. The Brownian ratchet model of cell extension generalized for microfilaments, microtubules and MSP filament (see below). Subunit recycling is achieved for microfilaments and microtubules by nucleotide hydrolysis and exchange and by monomer activation in the case of MSP. The plasma membrane is free to diffuse or oscillate from left to right under the influence of thermal motion. Movement in other directions is impeded. If the plasma membrane makes an excursion to the left, i.e. in the direction of cell movement, a subunit is free to add to the fast growing end of the filament. The plasma membrane can no longer return to its previous position as the subunit now occupies that space. The maximum force can be calculated where kB is Boltzmann's constant; T is the absolute temperature; D is the distance by which a subunit extends the polymer and Kon and Koff are the on and off rates of subunit assembly, respectively.
Figure 6. Treadmilling of microfilaments in the cell. Actin subunits polymerize at the leading edge, move down the filaments towards the cell body where their depolymerization is accelerated by cofilins. Monomeric actin released from the filaments then diffuses to the leading edge to complete the cycle. (a) An individual filament is highlighted in grey at time zero. (b) Some time later, the cell has moved towards the top of the page, and the original filament has grown by an amount equal to that of the cell movement by the addition of ‘new’ microfilament growth as the bottom of this filament is lost due to cofilin accelerated depolymerization.
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Maciver, Sutherland K(Apr 2001) Polymerization Dynamics of Cytoskeletal Filaments. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001254]