25.11:
Actin Polymerization
Actin polymerization can occur spontaneously or through actin-binding proteins.
Spontaneous actin polymerization has three phases: nucleation, elongation, and steady-state.
During nucleation, three actin monomers assemble into an actin nucleus.
In elongation, monomers are rapidly added to either end of the nucleus forming a filament. The end with faster addition of monomers is termed the plus-end or barbed-end, and the other is the minus-end or pointed-end.
At steady-state, the rates of monomer addition and filament disassembly are equal.
Actin-binding protein-mediated polymerization requires two proteins, profilin, and formin.
Profilin binds ADP-bound G-actin monomers and catalyzes ADP/ATP exchange forming ATP-G-actin-profilin complexes.
Formin has a thread-like FH1 domain that binds ATP-G-actin-profilin complexes and a donut-shaped FH2 domain that binds F-actin.
FH2 removes the capping protein from the plus-end of F-actin to allow the ATP-G-actin-profilin complexes from the FH1 domain to bind the uncapped-F-actin.
Upon binding, the ATP-G-Actin-profilin complex undergoes ATP hydrolysis, releasing profilin and allowing rapid actin polymerization at the plus-end of the filament.
25.11:
Actin Polymerization
Actin polymerization occurs through the head-to-tail association of binding sites on monomeric actin or G-actin to form filamentous or F-actin. The polymerization can be divided into three phases ̶ nucleation, elongation, and steady-state phase.
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight actin filaments with the help of actin-profilin complexes. They can form clusters near the plasma membrane to initiate actin filament formation. While in the cytoplasm, they may participate in the elongation phase of pre-existing actin filaments. During elongation of actin filaments, formins remove the capping proteins and form a sleeve around the actin subunits. The removal of capping proteins involves the dimerization of formin in the shape of a donut and binding to a pre-existing filament through the formin homology 2 or FH2 domain. Additionally, the FH1 domains of formin monomers also capture the profilin-G-actin complexes, thereby promoting the addition of G-actin to the filament.
Suggested Reading
- Kudryashov, D. S., & Reisler, E. (2013). ATP and ADP actin states. Biopolymers, 99(4), 245–256. https://doi.org/10.1002/bip.22155
- Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000. Section 18.2, The Dynamics of Actin Assembly. Available from:https://www.ncbi.nlm.nih.gov/books/NBK21594/