Actin-cross-linking proteins

The leucine zipper DNA-binding proteins, described in Chapter 10, are examples of globular proteins that use coiled coils to form both homo- and heterodimers. A variety of fibrous proteins also have heptad repeats in their sequences and use coiled coils to form oligomers, mainly dimers and trimers. Among these are myosin, fibrinogen, actin cross-linking proteins such as spectrin and dystrophin as well as the intermediate filament proteins keratin, vimentin, desmin, and neurofilament proteins. 

Although many cellular proteins are potential targets for phosphorylation by PKC, the myristoylated alanine-rich protein kinase C substrate (MARCKS) appears to be a major in vivo substrate. MARCKS is an acidic filamentous actin cross-linking protein that is found in high concentrations at presynaptic junctions and that is directed to... 

Dimeric S100P was found to bind and activate ezrin, a membrane/F-actin cross-linking protein (Koltzscher et al., 2003) possibly influencing cell morphology. 

Way M, Sanders M, Garcia C et al. Sequence and domain organization of scruin, an actin-cross-linking protein in the acrosomal process of Limulus sperm. J Cell Biol 1995 128(l-2) 51-60. 

Brink M, Gcrisch G, Iscnbcrg G ct al. A Dictyostclium mutant lacking an F-actin cross-linking protein, the I20-kD gelation factor J Cell Biol 1990 111 1477 89-... 

Fcchheimer M, Taylor DL. Isolation and characterization of a 30,000-dalton calcium-sensitive actin cross-linking protein from Dictyostelium discoideum. J Biol Chem 1984 259 4514-20. 

A FIGURE 19-5 Actin cross-linking proteins bridging pairs of actin filaments, (a) When cross-linked by fimbrin (red), a short protein, actin filaments pack side by side to form a bundle. 

Branching Is stimulated by the WASp family of proteins under the control of the Rho GTPases. Actin cross-linking proteins such as fllamin stabilize the branched network, whereas actin-severing proteins such as cofilin disassemble the branched structures. 

The molecular mechanisms that couple the contractile filaments to the dense bodies are not established. Dense bodies contain the actin-cross-linking protein, a-actinin, as do the Z-lines of skeletal muscle. Dense bodies also contain actin and probably calponin, although it is currently unclear whether the a and y ("smooth muscle ) isoforms of actin (See Section 4.2) are both present in dense bodies or only the p "non-muscle" isoform (Small 1995, North et al 1994a, 1994b, Mabuchi et d 1996). Ultras-tructural and biochemical data obtained by Mabuchi et al (1997) suggests that one function of calponin may be to couple actin filaments and intermediate filaments at dense bodies. 

ACTIN FILAMENT CROSS-LINKING PROTEIN/BUNDLING... 

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

Microtubule-actin cross-linking factor 1, isoform b Q96PK2 (h) 1) MACFIb 2) MACF1, isoform 4 3) Actin cross-linking family protein 7 (ACF7) MACF1 (h) 1 p32-p31 (h) 5938 (h)... 

Cross-linking proteins are placed into three gn>ups. Group I proteins have unique actin-binding domains Croup II have a 7.0(X. M V act in-binding domain and Group III have pairs of a 26,()(MI-MW actin-binding domain. 

Cytochalasins, drugs that inhibit cellular processes that require actin polymerization and depolymerization (e.g., phagocytosis, cytokinesis, clot retraction, etc.), also act by severing and capping actin filaments. Actin filaments can be stabilized by phalloidin, derived from the poisonous mushroom Amanita phalloides. Assembly of actin filaments into bundles (as in microvilli) and three-dimensional networks is accomplished by two groups of cross-linking proteins (Table 21-6). 

Microfilaments, which are small (5-7 nm in diameter) fibers composed of the protein actin, perform their functions by interacting with certain cross-linking proteins. Important roles of microfilaments include involvement in cytoplasmic streaming (a process that is most easily observed in plant cells in which cytoplasmic currents rapidly displace organelles such as chloroplasts) and ameboid movement (a type of locomotion created by the formation of temporary cytoplasmic protrusions). 

Actin filaments are organized into bundles and networks by a variety of bivalent cross-linking proteins (see Figure 19-5). 

The classic example of a myristoylated protein is the MARCKS protein (myristoylated alanine-rich C kinase substrate). MARCKS is an actin filament cross-linking protein regulated by PKC and calcium-calmodulin (Aderem el al., 1988 Hartwig et al, 1992). Myristoylation of MARCKS is required for effective binding to the actin network at the plasma membrane (Thelen et al.,... 

Actin polymers form the thin filaments (also called microfilaments) in the cell that are organized into compact ordered bundles or loose network arrays by cross-linking proteins. Short actin filaments bind to the cross-linking protein spectrin to form the cortical actin skeleton network (see Fig. 10.6). In muscle cells, long actin fdaments combine with thick filaments, composed of the protein myosin, to produce muscle contraction. The assembly of G-actin subunits into polymers, bundling of fibers, and attachments of actin to spectrin and to the plasma membrane proteins and organelles, are mediated by a number of actin-binding proteins and G-proteins from the Rho family. 

The assembly of F-actin filaments into stable networks and dynamic bundles (essential for myosin-based motility) is mediated by cross-linking agents such as a-actinin or actin-binding proteins such as fascin, fimbrin, and filamin [71, 77]. Even in the absence of any cross-linking proteins, nanofibrils of F-actin can associate with each other to form gels [78, 79]. 

In cooperation with many kinds of actin-binding proteins, the G-F transformation of actin generates translational movement of a bacterial cell in a host cell, as in Figure 10 [46], Anchoring and nucleation proteins, depolymerizing proteins, and cross-linking proteins work to make possible a fast cycle of actin molecules from one end of F-actin to the other end, that is, tread-milling. This system has been artificially reconstructed in vitro [47]. 

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