Caldesmon actin interactions

Apart from the phosphorylation theory, other regulatory mechanisms have also been suggested for smooth muscle contraction. A thin-filament protein that has been proposed as a regulatory component is caldesmon [102], Purified caldesmon is a potent inhibitor of actin-tropomyosin interaction with myosin. The mechanisms by which calcium removes this inhibition are controversial. Furthermore, phosphorylation of caldesmon by a caldesmon kinase in vitro has also been implicated in this... 

Sobue, K., Morimoto, K., Inui, M., Kanda, K. and Kakiuchi, S. (1982). Control of actin-myosin interaction of gjzzard smooth muscle by calmodulin- and caldesmon-linked flip-flop mechanism. Biomed. Res. 3, 188-196. 

There is considerable controversy over whether calponin and caldesmon interact on the same filament in vivo. In vitro, calponin competes with caldesmon for closely spaced sites on the actin molecule and there is evidence that the two do not complex on the same filament (Makuch et al 1991, Mezgueldi et al 1992), In addition, the inhibitory effects of calponin and caldesmon on actin-activated ATPase activity appear to be unaffected by each others presence. These observations seem to support ultrastructu-ral evidence that these proteins may localize to different actin filaments or different locations on the same filament (North et al 1994a, Makuch et al 1991) (see Section 4.2.2). 

Mabuchi K, Lin JJ, Wang CL (1993) Electron microscopic images suggest both ends of caldesmon interact with actin filaments. J Muscle Res Cell Motil 14 5464 Mabuchi K, Wang CL (1991) Electron microscopic studies of chicken gizzard caldesmon and its complex with calmodulin. J Muscle Res Cell Motil 12 145151... 

Fuji T, Machino K, Andoh H, et al. Galcium-dependent control of caldesmon-actin interaction by SlOO protein. J Biochem. 1990 107 133-137. 

In the smooth muscle cell, CD is incorporated into the thin filaments in the "contractile domain" of the cell (Furst et al., 1986 North et al., 1994a). Ultrastruc-tural studies presented in Chapter 4 (this volume) have shown that CD is located in the thin filament in an extended form beside TM along the axis of the actin double helix. The model (Fig. 2) places CD in potential contact with actin and TM throughout its length and allows a possible end-to-end interaction. These structural arrangements form the basis of caldesmon function in the thin filament. 

The basis of the proposed regulatory function of caldesmon is its ability to inhibit the interaction of myosin with the thin filament. A prerequisite for this is that CD binds to actin. In the native thin filament, TM is also present, and it is found that the presence of TM has effects on CD binding to actin and a very pro-... 

To account for activation of arterial smooth muscle independently of LC20 phosphorylation, attention has been focused on the possible roles of the thin filament-associated regulatory proteins, caldesmon and calponin. Both proteins have been localized in the actomyosin domain of the smooth muscle cell and both have been shown to inhibit actin-activated myosin ATPase by interacting with F-actin, tropomyosin, and/or myosin (Clark et al., 1986 Takahashi et al.,... 

Caldesmon has also been shown to inhibit tension development in chemically permeabilized gizzard smooth muscle (Pfitzer etal., 1993). Furthermore, inhibition of caldesmon/F-actin interaction in permeabilized VSM resulted in contractile force generation independently of changes in [Ca +J, supporting the concept that caldesmon may function as a regulator in situ independently of LC20 phosphorylation (Katsuyama et al., 1992). Both caldesmon (Adam et al.,... 

Ultrastructural studies of isolated chicken gizzard thin filaments localized caldesmon on the thin filament beside tropomyosin, arranged continuously along the axis of the actin double helix (Moody et al 1990, Vibert et al 1993, I hman et al 1997). In smooth muscle filaments derived from vascular or visceral tissue, the stoichiometry of caldesmon to tropomyosin and actin has been determined to be 1 2 14 (Lehman et al 1989, Marston 1990, Lehman et al 1993). Marston and Redwood (1991) proposed that each caldesmon molecule is placed in register with tropomyosin and extends for 78 nm, the length of two tropomyosin molecules. Each caldesmon molecule interacts with 14 actin monomers. This would result in a filament without radial symmetry such that different parts of the caldesmon molecule would appear on the same side of the actin filament. 

Marston SB, Fraser ID, Huber PA (1994) Smooth muscle caldesmon controls the strong binding interaction between actin-tropomyosin and myosin. J Biol Chem 269 3210432109... 

Tanaka T, Ohta H, Kanda K, Tanaka T, Hidaka H, Sobue K (1990) Phosphorylation of high-Mr caldesmon by protein kinase C modulates the regulatory function of this protein on the interaction betvreen actin and myosin. Eur J Biochem 188 495-500 Tanner JA, Haeberle JR, Meiss RA (1988) Regulation of glycerinated smooth muscle contraction and relaxation by myosin phosphorylation. Am J Physiol 255 C34-C42 Tansey MG, Hori M, Karaki K, Kamm KE, Stull JT (1990) Okadaic acid uncouples myosin light chain phosphorylation and tension in smooth muscle. FEBS Lett 270 219-221... 

Calponin [119] and caldesmon [120] are two thin filament associated proteins that bind to F-actin, tropomyosin and calmodulin. Interaction of 34 kDa calponin with F-actin and tropomyosin takes place in a Ca +-inde-pendent manner, whereas that with calmodulin is regulated in a Ca -de-pendent manner. The key role of calponin and caldesmon in SM is to down-regulate actomyosin ATPase activity in vitro [120,121]. Thus, they may participate in regulation of contractile performance. Despite their apparent functional similarity, sequence analysis indicates that calponin and caldesmon are not related proteins. They act by different mechanisms... 

SM) a-actin, myosin heavy chain and caldesmon. In attempts to engineer blood vessels using bioreactor systems, interactions between ECs and SMCs (e.g., EC adhesion to and lining of the inner lumen in contact with cultured SMCs) have improved by subjecting the system to proper mechanical stim-uh. In addition, cyclic strain has been shown to induce stem cell differentiation in SMCs (Park, 2007). 

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