Actin remodeling

Actin remodeling is the biochemical process that allows for the dynamic alterations of cellular organization. The remodeling of actin filaments occurs in a cyclic pattern on cell surfaces and exists as a fundamental aspect to cellular life. During the remodeling process, actin monomers polymerize in response to signaling cascades that stem from environmental cues. The cell's signaling pathways cause actin to affect intracellular organization of the cytoskeleton and often consequently, the cell membrane. Again triggered by environmental conditions, actin filaments break back down into monomers and the cycle is completed. Actin-binding proteins (ABPs) aid in the transformation of actin filaments throughout the actin remodeling process. These proteins account for the diverse structure and changes in shape of Eukaryotic cells. Despite its complexity, actin remodeling may result in complete cytoskeletal reorganization in under a minute. Actin remodeling is the biochemical process that allows for the dynamic alterations of cellular organization. The remodeling of actin filaments occurs in a cyclic pattern on cell surfaces and exists as a fundamental aspect to cellular life. During the remodeling process, actin monomers polymerize in response to signaling cascades that stem from environmental cues. The cell's signaling pathways cause actin to affect intracellular organization of the cytoskeleton and often consequently, the cell membrane. Again triggered by environmental conditions, actin filaments break back down into monomers and the cycle is completed. Actin-binding proteins (ABPs) aid in the transformation of actin filaments throughout the actin remodeling process. These proteins account for the diverse structure and changes in shape of Eukaryotic cells. Despite its complexity, actin remodeling may result in complete cytoskeletal reorganization in under a minute. Actin remains one of the most abundant proteins in all of Eukarya and is an enzyme (ATPase) that gradually hydrolyzes ATP. It exists in two forms within eukaryotic cells: globular or G-actin and filament/filamentous or F-actin. Globular actin is the monomeric form of the protein while the filamentous actin is a linear polymer of globular subunits. The assembly of filamentous actin arises as a result of weak, noncovalent interactions between G-actin and appears in the arrangement of a two-stranded asymmetrical helical polymer. 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'. 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. 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 thermodynamically favored for the addition of G-actin and kinetically dynamic as well. Simultaneously, older G-actin monomers 'fall off' of the pointed end of the microfilament. At the 'pointed end' of the F-actin polymer, actin monomers are bound to ADP, which dissociates more readily and rapidly than ATP-bound actin, which is found at the 'barbed end' of the polymer. Thus, in environments with high concentrations of free actin subunits, filamentous growth at the 'barbed end' remains greater than that of the 'pointed end'. This 'tread-milling', essentially exists as a simplified explanation of the actin remodeling process. 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. 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, diffusion-regulated actin polymerization of subunits bound to actin-monomer-sequestering proteins control initiation. Thymosin and Profilin both exist as actin-monomer-sequestering proteins that maintain the ability to limit spontaneous nucleation from occurring, thus halting the actin remodeling process and returning the cycle to its first step. Additionally, the cell utilizes polyphosphoinositides to aid in the removal of all known 'barbed end' capping proteins. Possible Mechanisms: Elongation