Overview of Cell Biology/Actin-Binding Proteins

Readings

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Actin-Binding Proteins

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Assembly of pure actin in vitro is different from cellular actin. F-actin is depolymerized by dilution in a low salt buffer.

Functions of Actin-Binding Proteins

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Monomer Binding Proteins

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The concentration of G-actin in the cell is about 200 μM (REMEMBER that the Cc of actin is 0.2 μM). Actin is maintainted as a monomer by sequestering proteins such as Thymosin b4 and Profilin.

Nucleating Proteins

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Nucleating proteins promote polymerization and are usually present in areas that undergo dynamic extension/retration. One key nucleating factor in cells is the Arp2/3 Complex which works in conjuction with the nucleation proting factor family of WASPs. The Arp2/3 and WASP nucleating activity form a filament that is capped at the (-) end of the filament. Another family of nucleating factors are formins, which nucleate in a way that leaves both ends of the polymer free to bind new monomers.

Capping Proteins

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Capping proteins stabilize filaments by capping to one end and preventing the addition or loss of new subunits.

Examples:

- CapZ caps at the (+) end.

- Tropomodulin binds at the (-) end.

- Tropomyosin binds along the length of the filament.

Severing and Depolymerizing Proteins

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A protein called ADF-cofilin binds to ADP associated monomers and then severing filaments and acclerating depolymerization of ADP actin from the minus ends. ADF-cofilin proteins are regulated in cells by phosphorylatin via LIM kinase.

During ameboid motility, cytosol flos from the center of the amoeba and turns into a gel when it reaches the front of the cell. The gel is turned to sol by gelsolin which severs actin filaments. After being severing, gelsolin remains bound to the (+) end of the filament. Gelsolin is inactive when Ca2+ concentrations in the cytoplasm are low

Networking and Bundling Proteins

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Proteins with shorter spacers tend to bundle filaments into parallel arrays. Crosslinking proteins tend to have longer spacers and arrange filaments in networks.

Examples of bundling proteins: fascin, villin, fimbrin, α-actinin

Examples of crosslinking proteins: spectrin, dystrophin, filamin

Cross-linking at the Plasma Membrane
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In muscle cells, cytoskeleton is linked to the membrane by dystrophin. Dystrophin was discovered as the gene mytated in Duchenne muscular dystrophy. Dystrophin binds to a membrane glycoprotein complex and stabilizes muscle plasma membrane.