Actin Capping protein

Stress fibers are parallel bundles of actin filaments that develop in the cytoplasm of fibroblasts from the cortical actin network in response to mechanical tension. These often bind to the plasma membrane at focal contacts and, through transmembrane linker glycoproteins, to the extracellular matrix. Thus, actin filaments of stress fibers indirectly Join to the inner face of the plasma membrane through molecular assemblies of attachment proteins, which include an actin-capping protein, a-actinin, vinculin, and talin (Small, 1988). 

Weeds, A.G., Maciver, S.K. (1993). F-actin capping proteins. Curr. Opin. Cell Biol. 5, 63-69. 

Wilkins and Lin (1982) claimed that vinculin is an actin capping protein. However, highly purified preparations of vinculin do not have such a capping action at all (Evans et al., 1984). It has also been reported that such a purified vinculin does not bundle actin filaments either (Ohtaki et al, 1986). Therefore, it is likely that some proteins other than vinculin are needed to make actin filaments attach to the cell membrane. 

Heiss, S.G. and Cooper, J.A. (1991). Regulation of capZ, an actin capping protein... 

Klenchin, V.A., Allingham, J.S., King, R., Tanaka, Marriott, G., and Rayment, I. (2003) Trisoxazole marrolide toxins mimic the binding of actin-capping proteins to actin. Nat. Struct. Biol, 10,1058-1063. 

Barbed-end-capping proteins (gelsolin and villin, 95 kD) attach to this specific end of the actin filament and inhibit the further addition of actin molecules. 

Pointed-end-capping proteins are acumentin (65 kD), spectrin (220-260 kD), and p-actinin (37 kD). They also regulate the length of actin filaments. 

Figure 2 The actin-ADP-ribosylating toxins, (a) Molecular mode of action. The actin-ADP-ribosylating toxins covalently transfer an ADP-ribose moiety from NAD+ onto Arg177 of G-actin in the cytosol of targeted cells. Mono-ADP-ribosylated G-actin acts as a capping protein and inhibits the assembly of nonmodified actin into filaments. Thus, actin polymerization is blocked at the fast-growing ends of actin filaments (plus or barbed ends) but not at the slow growing ends (minus or pointed ends). This effect ultimately increases the critical concentration necessary for actin polymerization and tends to depolymerize F-actin. Finally, all actin within an intoxicated cell becomes trapped as ADP-ribosylated G-actin.

Figure 3. Critical concentration behavior of actin self-assembly. For the top diagram depicting the macroscopic critical concentration curve, one determines the total amount of polymerized actin by methods that measure the sum of addition and release processes occurring at both ends. Examples of such methods are sedimentation, light scattering, fluorescence assays with pyrene-labeled actin, and viscosity measurements. Forthe bottom curves, the polymerization behavior is typically determined by fluorescence assays conducted under conditions where one of the ends is blocked by the presence of molecules such as gelsolin (a barbed-end capping protein) or spectrin-band 4.1 -actin (a complex prepared from erythrocyte membranes, such that only barbed-end growth occurs). Note further that the barbed end (or (+)-end) has a lower critical concentration than the pointed end (or (-)-end). This differential stabilization requires the occurrence of ATP hydrolysis to supply the free energy that drives subunit addition to the (+)-end at the expense of the subunit loss from the (-)-end.

Note that if a capping protein binds to monomeric actin, the capping protein will also be a monomer-sequestering agent. A good example of such behavior is profilin. See also ABM-1 ABM-2 Sequences inActin-Based Motors Actin-Based Bacterial Motility Actin Assembly Kinetics... 

ACTIN-BASED BACTERIAL MOTILITY ACTIN ASSEMBLY ASSAYS ACTIN ASSEMBLY KINETICS ACTIN FILAMENT CAPPING PROTEIN ACTIN FILAMENT SEVERING PROTEIN... 

ACTIN FILAMENT CAPPING PROTEIN Actin cross-linking/bundling,... 

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