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30.2:

Actin Polymerization and Cell Motility

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Cell Biology
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JoVE Core Cell Biology
Actin Polymerization and Cell Motility

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Cells must follow environmental cues and rearrange their internal components to migrate from one location to another.

This is primarily achieved through actin-filament reorganization at the cell's leading edge.

Actin is a multi-functional, globular protein that can polymerize to form polarized F-actin filaments with two distinguished ends – plus and minus.

They form a tough and flexible framework that supports and strengthens the cell membrane.

In response to appropriate signals, the actin monomers start assembling at the plus ends or branching at sides of existing filaments.

Simultaneously, the minus ends depolymerize and sever, releasing actin monomers that can be recycled back to the polymerizing end.

The continuous force generated by the directional polymerization of the actin filaments pushes the membrane outwards, forming membrane protrusions.

These protrusions help the cell to adhere to the matrix, sense their immediate environment, and allow forward cell displacement by retraction.

30.2:

Actin Polymerization and Cell Motility

Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.

Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate. This is achieved by forming different types of membrane protrusions, depending on the cell type and the extracellular signals. Primarily, cells move by recurrent cycles of protrusion and attachment of the cell front to the substratum, followed by detachment and retraction at their rear end.

The human genome encodes six highly conserved actin proteins—ACTC1, ACTA1, ACTA2, ACTG1, ACTG2, and ACTB; all expressed in different cell types. Mutations in any of these six actin genes or the genes encoding actin-binding proteins can lead to disease. For example, mutations in the ACTA1 gene can lead to muscle weakness, especially in the respiratory muscles, which can cause breathing difficulties — a condition called Nemaline Myopathy. Similarly, mutations in the WAS gene, a key regulator of actin filament nucleation, which is important for cell adhesion, chemotaxis, and phagocytosis of immune cells, causes Wiskott Aldrich syndrome in humans.

Suggested Reading

  1. Alberts et al., 6th edition; page 951
  2. Lodish et al., 8th edition; pages 811
  3. Ridley. A. Life at the Leading Edge. ScienceDirect. 2011; 145: 1012-1022. https://doi.org/10.1016/j.cell.2011.06.010
  4. Svitkina. T. The Actin Cytoskeleton and Actin-Based Motility. PMC. 2018; 10: 10.1101/cshperspect.a018267
  5. Inagaki N, and Katsuno H, Actin Waves: Origin of Cell Polarization and Migration?. Rev. Cell Biol. 2017; 7(27):515-526. https://doi.org/10.1016/j.tcb.2017.02.003
  6. Weiner O.D, et al. An actin-based wave generator organizes cell motility. Plos Biol. 2007; 5: e221 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1945041/
  7. Ecker. N & Kruse. K, Excitable actin dynamics and amoeboid cell migration. Plos One. 2021; https://doi.org/10.1371/journal.pone.0246311
  8. Clainche. C & Carlier. M. Regulation of Actin Assembly Associated With Protrusion And Adhesion in Cell Migration. APS. 2008. https://doi.org/10.1152/physrev.00021.2007