Actin in Neurons

The Properties of Actin in Neurons

Actin is the conserved globular protein with a molecule weight of 42 kD. Actin is widely expressed in almost all tissues and plays an important role in cell division, motility, and adhesion. In neurons, actin comprises about 4-5% of total protein and this value can be increased to 7-8% during brain development There are three actin isoforms in mammals, including α, β, and γ, of which α and mostly β are expressed in neurons. Actin filaments are thin polymers of actin protein. In this case, actin exists as soluble monomers (G-actin) as well as actin filaments (F-actin). In mature axons, a network of sub-axolemmal F-actin provides a substrate for cargos transport in short-distance, as well as stability for membrane integrity.

Fig.1 The neuronal actin cytoskeleton and how it gets regulated by external factors.¹

Functions of Actin in Neurons

F-actin organization can be regulated by a variety of actin-binding proteins (ABPs). ABPs are the focus of complex extrinsic and intrinsic signaling pathways. Some ABPs are expressed ubiquitously, such as ADF/cofilin, b-thymosin, and spectrin. There are also a variety of tissue specific ABPs, including muscle proteins Xin, myopodin, and drebrin A. In developing neurons, the F-actin dynamics can largely mediate axonal morphogenesis, collateral branching, axonal shape, branch retraction, and axonal regeneration. ABPs play key roles in complex intrinsic and extrinsic signaling pathways, and the defective regulation may result in multiple neurological pathologies and dysfunctions.

Studies have shown that many neurological diseases arise from defective regulation of ABP function. For example, the genetic defects in ABP regulation of growth cone actin result in defective axonal connectivity and further mental retardation and behavioral disorders. A better understanding of the complex mechanisms by which ABP determines actin organization will help develop treatments for neuronal diseases.

Functions and Samples of ABPs for Actin

• Sequester, or bind G-actin subunits. (β-thymosin)
• Nucleate actin polymerization. (Arp2/3 complex)
• Cap F-actin barbed ends to inhibit polymerization. (capZ)
• Cap pointed ends to inhibit depolymerization. (Tropomodulin)
• Bind barbed ends to inhibit capping. (ena-Drosophila)
• Bind pointed ends to promote depolymerization. (actin depolymerizing factor)
• Bundle, crosslink, or stabilize F-actin. (filamin)
• Sever actin filaments. (ADF/cofilin)
• Move cargo along actin filaments. (multiple myosin motors)
• Anchor F-actin to other cellular components (spectrin)

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References

1. Konietzny, A.; et al. Dendritic actin cytoskeleton: structure, functions, and regulations. Frontiers in cellular neuroscience. 2017, 11: 147. Distributed under Open Access license CC BY 4.0, without modification.