Question

Briefly summarise the process of treadmilling in the function of actin filaments.

Answer 1

Treadmilling is a phenomenon observed in many cellular cytoskeletal filaments, especially in actin filaments and microtubules. It occurs when one end of a filament grows in length while the other end shrinks resulting in a section of filament seemingly "moving" across a stratum or the cytosol. This is due to the constant removal of the protein subunits from these filaments at one end of the filament while protein subunits are constantly added at the other end.

process of treadmilling in the function of actin filaments:-

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 and the minus 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. Cofilin functions by binding to ADP-actin on the negative end of the filament, destabilizing it, and inducing depolymerization. Profilin induces ATP binding to G-actin so that it can be incorporated onto the positive end of the filament.

Critical concentration

The critical concentration is the concentration of G-actin (actin) at which the end will remain in an equilibrium state with no net growth or shrinkage. What determines whether the ends grow or shrink is entirely dependent on the cytosolic concentration of available monomer subunits in the surrounding area. Critical concentration differs from the positive (C_C⁺) and the negative end (C_C⁻), and under normal physiological conditions, the critical concentration is lower at the positive end than the negative end. Examples in how the cytosolic concentration relates to the critical concentration and polymerization are as follows:

• A cytosolic concentration of subunits above both the C_C⁺ and C_C⁻ ends results in subunit addition at both ends
• A cytosolic concentration of subunits below both the C_C⁺ and C_C⁻ ends results in subunit removal at both ends

Note that the cytosolic concentration of the monomer subunit between the C_C⁺ and C_C⁻ 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.

main function of actin filaments in macrophage

Directed crawling motion of cells such as macrophages relies on directed growth of actin filaments at the cell front.