Actin remodeling

Actin remains one of the most abundant proteins in all of Eukarya and is an

The asymmetrical nature of F-actin allows for distinct binding specificities at each terminus. The terminus that presents an actin subunit with an exposed ATP binding site is commonly labeled the "(−) end". Whereas, the opposite end of the polymer that presents a cleft and lacks a free ATP binding site is referred to as the "(+) end".^[2] Additionally, the respective ends of the actin microfilament are often specified by their appearance under transmission electron microscopy during a technique known as "decoration", where the addition of myosin results in distinctive actin-myosin binding at each terminus. The terms "pointed end" and "barbed end" refer to the "(−) end" and "(+) end" respectively.^[3]

Within the cell, the concentrations of G-actin and F-actin continuously fluctuate. The assembly and disassembly of F-actin is regularly known as "actin tread-milling". In this process, G-actin subunits primarily add to the "barbed end" of the filamentous polymer. This end proves to be both more

Cell surface (cortical) actin remodeling is a cyclic (9-step) process where each step is directly responsive to a cell signaling mechanism. Over the course of the cycle, actin begins as a monomer, elongates into a polymer with the help of attached actin-binding-proteins, and disassembles back into a monomer so the remodeling cycle may commence again.^[1][5] The dynamic function of actin remodeling is directly correlated to the immense variability of cell shape, structure, and behavior.

Initiation

Consists of a number of different possible mechanisms that ultimately determine where and when actin filament elongation is to occur. In the mechanism that involves the uncapping of the barbed-end,

• De novo nucleation by the Arp2/3 complex, formins, and Spire that forms a trimer^{[3][failed verification]}
• Barbed-end uncapping by the removal of barbed-end-capping proteins (CapZ, Hsp70, EPS8)^[1]
• Barbed-end uncapping by actin-binding-proteins that sever actin filaments^[1]

Elongation

Facilitated in vivo by polymerization promoters and barbed-end capping inhibitory proteins. The elongation phase begins when the concentration of short, F-actin polymers is significantly larger than at equilibrium.^[7] At this point, both termini accept the addition of new monomers (although primarily at the "barbed end") and the actin microfilament lengthens.^[4]

Termination

Involves the degradation of polyphosphoinositides and reactivation of "barbed end" capping proteins Hsp70 and CapZ, thereby reinitiating barbed-end capping and greatly diminishing elongation. Despite the presence of active capping proteins, certain inhibitors including profilin, formins, ENA and VASP promote elongation.^[6] These inhibitors may function in a variety of different methods, however, most employ the inhibition of subunit depolymerization and actin-depolymerizing actin-binding-proteins.^[1]

Branching amplification

Consists of the nucleation of new actin microfilaments from the existing sides of F-actin. The cell employs Arp2/3 complex to temporarily bind to existing polymers at a 70° angle. The Arp2/3 complex then elongates into a filamentous branch that proves essential for intracellular reorganization through cytoskeletal changes.

Attachment of the actin-orthogonal network to the cell's membrane proves essential to the locomotion, shape, and mechanical function of the cell. The dynamic nature of a cell remains directly related to the actin-filament network's ability to respond to the contractile forces that result from environmental and internal cues.[4]

Actin filament disassembly

The immobilization by interpenetration of actin filaments results from two distinct ABP families. The

Exists as the turnover point in the actin remodeling cycle. The proteins thymosin and profilin prevent the spontaneous nucleation of new actin trimers. The absence or inhibition of these proteins results in the cell's ability to commence the actin remodeling cycle and produce elongated F-actin.^[1]

See also

• Actin

References