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Caldesmon

Page updated 24/3/03

A 87kd protein principally from smooth muscle that binds F-actin in a calcium/calmodulin sensitive manner. Can bind actin filaments decorated with tropomyosin with which it is thought to regulated myosin in smooth and non-muscle tissues. Caldesmon is phosphorylated during mitosis by a cell-cycle dependent kinase (MPF) which dissociates caldesmon from the filaments.  Caldesmon also interacts with myosin and this is regulated by phosphorylated by casein kinase II (Wang & Yang, 2000).  In addition to binding actin, myosin calmodulin, caldesmon is also known to bind caltropin (Mani et al, 1992) and tubulin (Ishikawa et al, 1992). 

Actin-binding
A subject of controversy, it presently seems that caldesmon binds actin in a manner dependent on a number of conditions including the stoicheometry of caldesmon with actin (
Fredrickson et al, 2003).

 

Figure 1.  

A. Caldesmon binding to seven monomers B. Strong binding to only 3 monomers. C. Binding to one actin monomer. (Fredrickson et al, 2003).

References:-

Fredricksen, S., Cai, A., Gafurov, B., Resetar, A. & Chalovich, J. M. (2003) Influence of ionic strength. actin state, and caldesmon construct size on the number of actin monomers in a caldesmon binding site. Biochemistry. 42, 6136-6148.

Ishikawa, R., Kagami, O., Hayashi, C. and Kohama, K. (1992). Cell Mot.Cytoskeleton 23, 244-251.

Mani, R.S., McCubbin, W.D. and Kay, C.M. (1992). Biochemistry 31, 11896-11901.

Wang, Z. and Z. Q. Yang (2000). Casein kinase II phosphorylation of caldesmon downregulates myosin-caldsemon interaction. Biochemistry 39, 11114-11120.

Chalovich, J. M., Chen, Y.-d., Dudek, R. & Luo, H. (1995) Kinetics of binding of caldesmon to actin. J. Biol. Chem. 270, 9911-9916.

Szczesna, D., Graceffa, P., Wang, C.-L. A. & Lehrer, S. S. (1994) Myosin S1 changes the orientation of caldesmon on actin. Biochemistry. 33, 6716-6720.

Warren, K. S., Lin, J. L.-C., Wamboldt, D. D. & Lin, J. J.-C. (1994) Overexpression of human fibroblast caldesmon fragment containing actin-, Ca++/Calmodulin-, and tropomyosin-binding domains stabilizes endogenous tropomyosin and microfilaments. J.Cell Biol. 125, 359-368.

Medvedeva, M., Kolobova, E. A., Huber, P. A. J., Fraser, I. D. C., Marston, S. B. & Gusev, N. B. (1997) Mapping of contact sites in the caldesmon-calmodulin complex. Biochem. J. 324, 255-262.

Wang, Z., Yang, Z.-Q. & Chacko, S. (1997) Functional and structural relationship bewteen the calmodulin-binding, actin binding, and actomysoin-ATPase inhibitory domains on the C terminus of smooth muscle caldesmon.  J.Biol.Chem. 272, 16896-16903.

Nowak, E., Hinssen, H. & Dabrowska, R. (1993) Synergistic and antagonistic modulation of actomyosin ATPase by caldesmon, tropomyosin and gelsolin. J.Muscle Res.Cell Motil. 14, 244.

Huber, P. A. J. (1997) Caldesmon.  Int.J.Biochem.Cell Biol. 29, 1047-1051.

Sen, A. & Chalovich, J. M. (1998) Caldesmon-Actin-Tropomyosin contains two types of binding sites for myosin S1. Biochemsitry. 37, 7526-7531.

Bartegi, A., Roustan, C., Bertrand, R., Kassab, R. & Fattoum, A. (1998) Interaction of caldesmon with actin subdomain-2.  Eur.J.Biochem. 254, 571-579.

Scott-Woo, G. C., Walsh, M. P., Ikebe, M. & Kargacin, G. J. (1998) Identification and localization of caldesmon in cardiac muscle. Biochem.J. 334, 161-170.

Polyakov, A. A., Huber, P. A. J., Marston, S. B. & Gusev, N. B. (1998) Interaction of isoforms of S100 protein with smooth muscle caldesmon. FEBS letters. 422, 235-239.

McManus, M. J., Lingle, W. L., Salisbury, J. L. & Maihle, N. J. (1997) A transformation-associated complex invloving tyrosine kinase signal adapter protein and caldesmon links v-ErbB signaling to actin stress fiber disassembly. PNAS.USA. 94, 11351-11356.

Marston, S. B. & Redwood, C. S. (1993) The essential role of tropomyosin in cooperative regulation of smooth muscle thin filament activity by caldesmon. J.Biol.Chem. 268, 12317-12320.

Bárány, K., Polyák, E. & Bárány, M. (1992) Involvement of calponin and caldesmon in sustained contraction of arterial smooth muscle. BBRC. 187, 847-852.

Shirinsky, V. P., Biryukov, K. G., Mettasch, J. H. & Sellers, J. R. (1992) Inhibition of the relative movement of actin and myosin by caldesmon and calponin. J.Biol.Chem. 267, 15886-15892.

Winder, S. J., Sutherland, C. & Walsh, M. P. (1992) A comparison of the effects of calponin on smooth and skeletal muscle actomysoin systems in the presence and absence of caldesmon. Biochem.J. 288, 733-739.

D'angelo, G., Graceffa, P., Albert Wang, C.-L., Wrangle, J. & Adam, L. P. (1999) Mammal-specific, ERK-dependent, caldesmon phosphorylation in smooth muscle. J.Biol.Chem. 274, 30115-30121.

Dabrowska, R., Hinssen, H., Galazkiewicz, B. & Nowak, E. (1996) Modulation of gelsolin-induced actin-filament severing by caldesmon and tropomyosin and the effect of these proteins on the actin activation of myosin mg2+-atpase activity. Biochemical Journal. 315, 753-759.

Foster, D. B., Shen, L.-H., Kelly, J., Thibault, P., Van Eyk, J. E. & Mak, A. S. (2000) Phosphorylation of caldesmon by p21-activated kinase. J.Biol.Chem. 275, 1959-1965.

 Leszyk, J., Mornet, D., Audemard, E. & Collins, J. H. (1989) Amino acid sequence of a 15 kilodalton actin-binding fragment of turkey gizard caldesmon; similarity with dystrophin, tropomyosin and the tropomyosin-binding region of troponin T. Biochem.Biophys.Res.Comm. 160, 210-216.

Wang, Z. & Yang, Z. Q. (2000) Casein kinase II phosphorylation of caldesmon downregulates myosin-caldsemon interaction.  Biochemistry. 39, 11114-11120.

 
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