Actin-associated protein

In addition to the major proteins of striated muscle (myosin, actin, tropomyosin, and the troponins), numerous other proteins play important roles in the maintenance of muscle structure and the regulation of muscle contraction. Myosin and actin together account for 65% of the total muscle protein, and tropomyosin and the troponins each contribute an additional 5% (Table 17.1). The other regulatory and structural proteins thus comprise approximately 25% of the myofibrillar protein. The regulatory proteins can be classified as either myosin-associated proteins or actin-associated proteins. 

R. J. Bloch, M. Velez, J. Krikorian, and D. Axelrod, Microfilaments and actin-associated proteins at sites of membrane-substrate attachment within acetylcholine receptor clusters, Exp. Cell Res. 182, 583-596 (1989). 

Actin-associated proteins. The cytoplasm contains more than 50 different proteins that bind specifically to G actin and F actin. Their actin uptake has various different functions. This type of bonding can serve to regulate the G actin pool (example profilin), influence the polymerization rate of G actin (vil-lin), stabilize the chain ends of F actin fragin, T-actinin), attach filaments to one another or... 

Fig. 4. Structure of striated muscle costameres and the DPC. A single membrane-associated costamere from a portion of a striated muscle fiber is magnified above to show the components of the dystrophin-associated protein complex that are involved in linking desmin intermediate filaments (IFs) to the muscle cell membrane. Additional actin-associated proteins present at these sites (including vinculin, talin, spectrin, and ankyrin) are not shown here. In addition to components of the DPC, plectin has also been localized to costameres, and likely contributes to linking desmin IFs to actin-associated structures.

M6. Mundel, P., Heid, H. W., Mundel, T. M., Kruger, M., Reiser, J., and Kriz, W., Synaptopodin An actin-associated protein in telencephalic denrites and renal podocytes. J. Biol. Chem. 139, 193-204 (1997). 

Another subsynaptic fraction derived directly from presynaptic specializations, the presynaptic particle fraction (PPF) can be separated from PSD by adjusting the pH of Triton X-100 extraction of isolated trans-synaptic scaffolds. As one might expect, it has been shown that the major proteins of the PPF, clathrin and dynamin, are concentrated in the presynaptic compartment (Phillips et al. 2005). These investigators used multidimensional protein identification technology (MudPIT) to compare the PPF and the PSD fraction. Of 341 proteins identified, 50 localized in the PPF, 231 in the PSD fraction, and 60 were found to be common to both fractions. The PPF was also characterized by a low proportion of actin and actin-associated proteins along with a high proportion of vesicle proteins. The authors concluded that the PPF consists of presynaptic proteins not cormected to the actin-based synaptic framework and that clathrin may be an anchorage scaffold for many presynaptic proteins. 

In recent years the biological importance of the cytoskeletal structures—microtubules, intermediate filaments, and microfilaments (actin)—has attracted the attention of many cell biologists. In striated muscle, myosin and actin filaments together with Z lines are the main cytoskeletal structures to form sarcomeres of the myofibril. However, myosin and actin are contractile proteins, and some of the proteins constituting the Z line are classified as actin-associated proteins. Therefore, cell membrane attachment proteins, intermediate filaments, and some other structural proteins are described in this section. There has not been any report on muscle microtubules, although their presence is shown in some electron micrographs of sectioned samples. 

What determines the binding specificity of actin-associated proteins in smooth muscle ... 

We are still much in the dark regarding CP function. Does it perform both structural and regulatory roles, and if so what are they Are these roles carried out in the cytoskeleton or in the contractile apparatus, or both Does CP influence or complement CD function And if Ca2+ binding proteins are the primary regulators, which one(s) operate on CP To determine the function of CP in vivo will require new approaches. In part because of the presence of multiple targets for Ca2+ binding proteins in smooth muscle (including MLCK, CD, and CP), it has so far proved difficult to define the relative roles that myosin and the actin-associated proteins play in smooth muscle. Here specifically, we will want to know what roles CD and CP perform in the process of tension maintenance... 

There are a number of actin-associated proteins proposed to be involved in the regulation of SM. These are discussed in the following sections and elsewhere in this volume. Although it remains debatable whether these proteins contribute to the regulation of the SM cross-bridge in vivo, there is ample biochemical evidence in which the activity of actomyosin preparations and in vitro motility assays are affected by caldesmon (CD), calponin (CP), and tropomyosin (TM), as well as several other proteins. 

Letoumeau, P.C. and Shattuck, T.A. (1989) Distribution and possible interactions of actin-associated proteins and cell-adhesion molecules of nerve growth cones. Development 105 505-519. 

In a living cell, there are many different specialized proteins for binding, btmdling, and otherwise modifying the network of filamentous proteins. In fact, more than 100 actin-associated proteins alone have been identified. Not only is it important to... 

Synaptopodin (formerly caUed pp44), a member of a family of actin-associated proteins rich in pro-line, was found in telencephahc dendrites and renal podocytes (Mundel et al. 1997). The cytoskeletal rearrangements of mouse podocyte clones are accompanied by the onset of synaptopodin synthesis. 

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