Actin polymerization and depolymerization in developing vertebrates

Abstract

Development is a complex process that occurs throughout the life cycle. F-actin, a major component of the cytoskeleton, is essential for the morphogenesis of tissues and organs during development. F-actin is formed by the polymerization of G-actin, and the dynamic balance of polymerization and depolymerization ensures proper cellular function. Disruption of this balance results in various abnormalities and defects or even embryonic lethality. Here, we reviewed recent findings on the structure of G-actin and F-actin and the polymerization of G-actin to F-actin. We also focused on the functions of actin isoforms and the underlying mechanisms of actin polymerization/depolymerization in cellular and organic morphogenesis during development. This information will extend our understanding of the role of actin polymerization in the physiologic or pathologic processes during development and may open new avenues for developing therapeutics for embryonic developmental abnormalities or tissue regeneration.

Keywords: F-actin; G-actin; embryonic development; morphogenesis; organogenesis.

FIGURE 1

Actin structure and polymerization pattern. (A) Crystal structure of the G-actin. The structure of native G-actin was retrieved from Protein Data Bank (PDB; ID: 3 hbt). The G-actin monomer contains four subdomains (SD1, SD2, SD3, and SD4) and the loop is centered at residue Lys336. The linker helix at residues Gln137–Ser145 functions as an axis of a hinge connecting the two major domains of actin, consequently forming two clefts between the domains. The upper cleft binds the nucleotide, whereas the lower cleft is the binding site for ABPs. (B) The structure of F-actin was retrieved from PDB (ID: 8a2r). F-actin is a double-stranded and right-handed helix. Actin flattening in subdomain 1 and 2 during the G-to F-actin transition is shown in crystal or cartoon forms. (C) Actin polymerization and depolymerization, in which ATP-G-actin is involved in polymerization into ATP-F-actin, and ATP-F-actin in actin filaments spontaneously dissociates into ADP ∼ Pi-F-actin. It then becomes ADP-F-actin and finally depolymerizes into ADP-G-actin to achieve the balance of polymerization and depolymerization. (D) Barbed ends of actin polymerize faster and the tips polymerize slower. The new branches of actin filaments form a 70° angle with the old filaments (Figures C and D demonstrate the functions of the six ABPs).

FIGURE 2

Actin is involved in various cellular physiological activities. (A) AJs form the intercellular junctions, and E-cadherin (red) form the intercellular contact. The cytoplasmic part of E-cadherin binds to β-catenin (green) and P120-catenin (red), and then β-catenin binds to α-catenin (blue). Finally, the -COOH terminus of α-catenin binds directly to F-actin (purple). (B) F-actin is indirectly attached to integrin via talin to ensure focal adhesion between cells and the ECM. (C) F-actin regulates the length of cell adhesion junctions and the formation of new adhesion junctions through polymerization and depolymerization. (D) Two types of actin aggregation: a pulsatile network and a persistent network. (E) The tendency of F-actin to depolymerize leads to increased cellular deformability, whereas the tendency to polymerize helps maintain cellular morphology. (F) The tendency of F-actin to depolymerize contributes to the reduction of adhesion between epithelial cells. The tendency to promote polymerization enhances the ability of cells to migrate and acquire a mesenchymal phenotype, in which actin polymerization at the anterior edge of migrating cells generates thrust, whereas actin filaments at the posterior edge generate contractile force together with myosin. Created with BioRender.com.