Actin

MEF microfilaments

STD Depth Coded Stack Phallodin Stained Actin Filaments

PDB 1unc EBI

Cardiac sarcomere structure

Sarcomere

Actin is a family of globular multi-functional proteins that form microfilaments. It is found in essentially all eukaryotic cells (the only known exception being nematode sperm), where it may be present at concentrations of over 100 μM. Actin participates in many important cellular processes, including muscle contraction, cell motility, cell division and cytokinesis, vesicle and organelle movement, cell signaling, and the establishment and maintenance of cell junctions and cell shape.

Structure

Actin is a highly conserved protein that is approximately 42 kDa in size and is composed of a single polypeptide chain. It has a globular structure (G-actin) that polymerizes to form filaments (F-actin), which are two-stranded helical polymers. The actin filament is dynamic, undergoing continuous polymerization and depolymerization.

Function

Actin's primary function is to generate mechanical force; this is achieved through ATP hydrolysis. In muscle cells, actin filaments slide past myosin filaments in a process known as the sliding filament theory of muscle contraction. In non-muscle cells, actin polymerization can drive cell movement, such as in amoeboid locomotion, and contribute to changes in cell shape.

Actin is also involved in various cellular processes that are critical for cell survival and function. These include providing structural support to the cell, enabling cytoplasmic streaming, segregating chromosomes during cell division, and facilitating signal transduction pathways.

Isoforms

In humans, the actin family comprises six isoforms, which are divided into three classes based on their isoelectric points: alpha (α), beta (β), and gamma (γ). Alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. Beta and gamma actins coexist in most cell types as components of the cytoskeleton and are involved in cell motility.

Regulation

The polymerization of actin is regulated by a plethora of actin-binding proteins, which can control the length of filaments, cap the ends of filaments, sever filaments, and nucleate the assembly of new filaments. Important regulatory proteins include profilin, which promotes actin assembly; cofilin, which disassembles filaments; and Arp2/3 complex, which nucleates the formation of branched actin networks.

Clinical Significance

Mutations in actin or actin-regulating proteins are associated with a variety of diseases, including muscle diseases, cardiomyopathies, and certain forms of deafness. Actin is also exploited by many microorganisms and viruses to invade and move within host cells.

Research

Actin is a subject of extensive research in cell biology and biophysics due to its fundamental role in cellular processes and its involvement in various diseases. Studies of actin have also contributed to the development of drugs that can influence actin dynamics, offering potential therapeutic strategies for diseases associated with actin dysfunction.