Actin and Actin Filaments

Davina Tondeleir, Ghent University, Ghent, Belgium
Joël Vandekerckhove, Ghent University, Ghent, Belgium
Christophe Ampe, Ghent University, Ghent, Belgium

Published online: November 2011

DOI: 10.1002/9780470015902.a0001255.pub3

Actin is an evolutionary conserved molecule that self assembles into long polymers. These filaments form the building block of the actin cytoskeleton. This system is one of the main engines enabling cell motility processes. In muscle cells stable actin filaments participate in contraction. In nonmuscle cells, however, the filaments are more dynamic and polymerisation of actin generates the force for the formation of cellular protrusions required for cell migration. Various actin-binding proteins orchestrate this dynamic turnover of actin filaments and thereby contribute to the different migration modes possible for nonmuscle cells. Next to its role in the cytoplasm actin also resides in the nucleus where it may regulate transcription in multiple ways. Because of its complexity, impaired regulation of the actin cytoskeleton disturbs cell function and deregulations of the actin machinery are associated with an increasing number of diseases such as myopathies and cancer.

Key Concepts:

  • Actins are conserved proteins with important functions during development and in adult life.
  • Actin self-assembles into structurally and kinetically polarised filaments.
  • Numerous actin-binding proteins regulate (dis)assembly and organise filaments in higher order structures.
  • Dynamic actin polymerisation drives multiple types of nonmuscle cell migration via formation of specific subcellular structures.
  • Actin cytoskeletal diseases are caused by mutations in actins or via disturbed regulation of the cytoskeleton.
  • In addition to its cytoplasmic function in cell motility processes, actin has a nuclear role in transcription.

Keywords: actin-binding proteins; cell motility; cytoskeleton; microfilament; polymerisation

Figure 1. Structure of monomeric and filamentous actin. (a) The structure of an actin monomer (Protein Depository Brookhaven code 3MFP, Fujii et al., 2010). The backbone is shown as a ribbon with the secondary structural elements in red (a-helices), cyano (b-strands), green (b-turns) and grey (loops). ATP (orange) and a divalent metal ion (not shown) bind in the cleft between the four subdomains of the molecule (1, 2, 3 and 4). The N- and C-termini are both located in subdomain 1. (b) The actin monomer is rotated 90° relative to the molecule shown in (a). In (a) and (b) residues that interact with other protomers are colour coded: blue interactions along the helix; pink across the helix (the residues protruding from the middle of the molecule (in b) on the right are part of the plug); the purple residue is involved in both types of contact. (c) The Holmes model of the helical actin filament (Protein Depository Brookhaven code 3G37, Murakami et al., 2010). 12 actin protomers, associated in a head-to-tail fashion, are depicted. If considered as a double-stranded, the right-handed helix strand is formed by the green protomers, the other strand is formed by the alternating blue and magenta protomers. The barbed end is at the bottom of the filament. Subdomain 1 is at the high radius as evidenced from the position of the N-terminus in the two lower protomers (N). Contacts are made between subdomains 2 (for numbering see (a)) and 4 from one protomer to subdomain 3 from the protomer above, along the filament and between subdomains 3 and 4 from one protomer to subdomains 2 and 3 from adjacent protomers across the helix, See also .
Figure 2. Actin polymerisation and actin-binding proteins. The actin cycle (lower part) and modulation by actin-binding proteins. ATP-actin (blue chevrons) will incorporate at the fast-growing ends (indicated with +). Protomers will hydrolyse ATP to ADP-Pi (dark blue chevrons) and subsequently release inorganic phosphate, yielding ADP-protomers (light blue chevrons). These dissociate from the other filament end (indicated with –) after which they exchange ADP for ATP. Several actin-binding proteins yellow modulate the cycle by typical activities (boxed green for explanation see text). Other actin-binding proteins mediate linkage to other filaments or to membranes or proteins.
Figure 3. Actin and actin-binding proteins in cells. The actin cytoskeleton of migrating fibroblasts (upper right). Actin is visualised by fluorescently labelled phalloidin (red) the cell has been additionally stained for mammalian enabled, MENA (green) (pictures courtesy of Dr Lambrechts, Department of Biochemistry, Ghent University). The lamellipodia (L), filopodia (F) and the tails (T) are indicated. All contain actin-rich structures. The dot-like structures formed by MENA staining are tips of microspikes. The arrow indicates the direction of migration. In the scanning electron micrograph of a moving fibroblast (lower right panel, picture courtesy of Heath J), the lamellipodium, filopodia and ruffles (R) are indicated. In the diagram of filaments in lamellipodia (upper left) and filopodia (lower left), the barbed end is oriented towards the membrane (blue line). In lamellipodia, the filaments run at different angles to each other; in filopodia they are parallel.
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 Further Reading
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    Visa N and Percipalle P (2010) Nuclear functions of actin. Cold Spring Harbor Perspectives in Biology 2: 1–13.

Related Sub-Topics:

Cell Cytoskeleton | Cell Motility | Protein Structure | Cell Motility and Transport | Protein Folding, Evolution and Degradation | Proteins: Structure, Function, Metabolism | Cell Structure | Biochemistry of Cell Motility
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Article Title: Actin and Actin Filaments
 
How to Cite close
Tondeleir, Davina, Vandekerckhove, Joël, and Ampe, Christophe(Nov 2011) Actin and Actin Filaments. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001255.pub3]