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Biochemistry of the Ca2+- and Calmodulin-Dependent Regulation of the Cytoskeleton

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Abstract

Following the discovery of calmodulin (Kakiuchi et al. 1969, 1970; Cheung 1970), it was proposed that the contractile device of smooth muscle and the cytoskeleton of nonmuscle tissues may be regulated by Ca2+/calmodulin. Recently, we have obtained considerable amounts of evidence to support the view that the regulatory actions of Ca2+/calmodulin are mediated by a number of specific calmodulin-binding proteins which also bind to F-actin filaments or to tubulin (Kakiuchi and Sobue 1983). Caldesmon (Sobue et al. 1981a, b) from smooth muscle and tau factor (Sobue et al. 1981c) from brain microtubules are calmodulin-binding proteins which also bind to F-actin or tubulin, respectively. The Ca2+-dependent binding of calmodulin to these proteins obviated the interaction between these proteins and F-actin or tubulin. Therefore, the binding of these proteins to calmodulin and cytoskeletal proteins alternates, depending on the concentration of Ca2+ (Fig. 1). As the binding of the calmodulin-binding proteins to the target cytoskeletal proteins modulates the function of the latter proteins, calmodulin regulates the function of cytoskeletal proteins via these calmodulin-binding proteins. We named this type of regulatory action of calmodulin flip-flop regulation (Kakiuchi and Sobue 1981, see also Kakiuchi and Sobue 1983). This article is a brief description of these calmodulin-binding proteins.

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References

  • Adelstein RS, Sellers JR, Conti MA, Pato MD, de Lanerolle P (1982) Regulation of smooth muscle contractile proteins by calmodulin and cyclic AMP. Fed Proc 41: 2873–2878

    PubMed  CAS  Google Scholar 

  • Baines AJ (1983) The spread of spectrin. Nature (Lond) 301: 377–378

    Article  CAS  Google Scholar 

  • Bennett V, Davis J, Fowler WE (1982) Brain spectrin, a membrane-associated protein related in structure and function to erythrocyte spectrin. Nature (Lond) 299: 126–131

    Article  CAS  Google Scholar 

  • Branton D, Cohen CM, Tyler J (1981) Interaction of cytoskeletal proteins on the human erythrocyte membrane. Cell 24: 24–32

    Article  PubMed  CAS  Google Scholar 

  • Cavadore JC, Molla A, Harricane MC, Gabrion J, Benyamin Y, Demaille JG (1982) Subcellular localization of myosin light chain kinase in skeletal, cardiac and smooth muscles. Proc Natl Sci USA 79: 3475–3479

    Article  CAS  Google Scholar 

  • Cheung WY (1970) Cyclic 3’,5’-nucleotide phosphodiesterase: demonstration of an activator. Biochem Biophys Res Commun 38: 533–538

    Article  PubMed  CAS  Google Scholar 

  • Cleveland DW, Hwo SY, Kirschner MW (1977) Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin. J Mol Biol 116: 207–225

    Article  PubMed  CAS  Google Scholar 

  • Cohen CM (1983) The molecular organization of the red cell membrane skeleton. Semin Hematol 20: 141–158

    PubMed  CAS  Google Scholar 

  • Dabrowska R, Hinkins S, Walsh MP, Hartshorne DJ (1982) The binding of smooth muscle myosin light chain kinase to actin. Biochem Biophy Res Commun 107: 1524–1531

    Article  CAS  Google Scholar 

  • Davies PJA, Klee CB (1981) Calmodulin-binding proteins: a high molecular weight calmodulinbinding protein from bovine brain. Biochem Int 3: 203–212

    CAS  Google Scholar 

  • Ebashi S, Nanomura Y, Nakamura S, Nakasone H, Kohama K (1982) Regulatory mechanism in smooth muscle: actin-linked regulation. Fed. Proc 41: 2863–2867

    PubMed  CAS  Google Scholar 

  • Glenney JR, Glenney P, Osborn M, Weber K (1982a) An F-actin and calmodulin-binding protein from isolated intestinal brush borders has a morphology related to spectrin. Cell 28: 843–854

    Article  PubMed  CAS  Google Scholar 

  • Glenney JR, Glenney P, Weber K (1982b) Erythroid spectrin, brain fodrin and intestinal brush-border proteins (TW-260/240) are related molecules containing a common calmodulin-binding subunit bound to a variant cell type-specific subunit. Proc Natl Acad Sci USA 79: 4002–4005

    Article  PubMed  CAS  Google Scholar 

  • Guerriero Jr V, Rowley DR, Means AR (1981) Production and characterization of an antibody to myosim light chain kinase and intracellular localization of the enzyme. Cell 27: 449–458

    Article  PubMed  CAS  Google Scholar 

  • Gshimura K, Ban T, Matsuda H, Fujita H, Sobue K, Kakiuchi S (1984) Immunocytochemical demonstration of caldesmon (a calmodulin-binding F-actin-interacting protein) in smooth muscle fibers and absorptive epithelial cells of the rat small intestine. Cell and Tissue Res 235: 207–209

    Google Scholar 

  • Kakiuchi S, Sobue K (1981) Ca2+ and calmodulin-dependent flip-flop mechanism in the micro-tubule assembly-disassembly. FEBS Lett 132: 141–143

    Article  PubMed  CAS  Google Scholar 

  • Kkiuchi S, Sobue K (1983) Control of cytoskeleton by calmodulin and calmodulin-binding proteins. Trends Biochem Sci 8: 59–62

    Article  Google Scholar 

  • Kakiuchi S, Yamazaki R, Nakajima H (1969) Studies on brain cyclic 3’,5’-nucleotide phosphodiesterase: its purification and properties (in Japanese). Bull Jpn Neurochem Soc 8: 17–20

    Google Scholar 

  • Kakiuchi S, Yamazaki R, Nakajima H (1970) Properties of a heat-stable phosphodiesterase activating factor isolated from brain extract: studies on cyclic 3’,5’-nucleotide phosphodiesterase. II. Proc Jpn Acad 46: 587–592

    CAS  Google Scholar 

  • Kakiuchi S, Sobue K, Fujita M (1981) Purification of a 240,000 dalton calmodulin-binding protein from a microsomal fraction of brain. FEBS Lett 132: 144–148

    Article  PubMed  CAS  Google Scholar 

  • Kakiuchi S, Sobue K, Kanda K et al. (1982a) Correlative biochemical and morphological studies of brain calspectin: a spectrin-like calmodulin-binding protein. Biomed Res 3: 400–410

    CAS  Google Scholar 

  • Kakiuchi S, Yasuda S, Yamazaki R, Teshima Y, Kanda K, Kakiuchi R, Sobue K (1982b) Quantitative determinations of calmodulin in the supernatant and particulate fractions of mammalian tissues. J Biochem (Tokyo) 92: 1041–1048

    CAS  Google Scholar 

  • Kakiuchi S, Sobue K, Morimoto K, Kanda K (1982c) A spectrin-like calmodulin-binding protein (calspectin) of brain. Biochem Int 5: 755–762

    CAS  Google Scholar 

  • Kakiuchi R, Inui M, Morimoto K, Kanda K, Sobue K, Kakiuchi S (1983) Caldesmon, a calmodulinbinding, F actin-interacting protein, is present in aorta, uterus and platelets. FEBS Lett 154: 351–356

    Article  PubMed  CAS  Google Scholar 

  • Kumagai H, Nishida E, Sakai H (1982) The interaction between calmodulin and microtubule proteins. (IV) Quantitative analysis of the binding between calmodulin and tubulin dimer. J Biochem (Tokyo) 91: 1329–1336

    CAS  Google Scholar 

  • de Lanerolle P, Adelstein RS, Feramisco JR, Burridge K (1981) Characterization of antibodies to smooth muscle myosin kinase and their use in localizing myosin kinase in nonmuscle cells. Proc Natl Acad Sci USA 78: 4738–4742

    Article  PubMed  Google Scholar 

  • Lazarides E, Nelson WJ (1982) Expression of spectrin in nonerythroid cells. Cell 31:505–508 Levine J, Willard M (1981) Fodrin: axonally transported polypeptides associated with the internal periphery of many cells. J Cell Biol 90: 631–643

    Google Scholar 

  • Means AR, Dedman JR (1980) Calmodulin: an intracellular calcium receptor. Nature (Lond) 285: 73–77

    Article  CAS  Google Scholar 

  • Morimoto K, Kambayashi J, Kosaki G, Kanda K, Sobue K, Kakiuchi S (1982) Calmodulin is the sole Ca2+-sensitizing factor in platelet myosin B. Biomed Res 3: 83–90

    CAS  Google Scholar 

  • Owada MK, Hakura A, Iida K, Yahara I, Sobue K, Kakiuchi S (to be published 1984 ) Occurrence of caldesmon (a calmodulin-binding protein) in cells: comparison of normal and transformed cells. Proc Natl Acad Sci USA

    Google Scholar 

  • Palfray HC, Schiebler W, Greengard P (1982) A major calmodulin-binding protein common to various vertebrate tissues. Proc Natl Acad Sci USA 79: 3780–3784

    Article  Google Scholar 

  • Shimooka T, Watanabe Y (1981) Stimulation of actomyosin Mg2+-ATPase activity by a brain microtubule-associated protein fraction. High-molecular weight actin-binding protein is the simulating factor. J Biochem (Tokyo) 90: 1297–1307

    CAS  Google Scholar 

  • Sobue K, Muramoto Y, Yamazaki R, Kakiuchi S (1979) Distribution in rat tissues of modulator-binding protein of particulate nature: studies with [3H]modulator protein. FEBS Lett 105: 105–109

    Article  PubMed  CAS  Google Scholar 

  • Sobue K, Fujita M, Muramoto Y, Kakiuchi S (1980) Spectrin as a major modulator binding protein of erythrocyte cytoskeleton. Biochem Int 1: 561–566

    CAS  Google Scholar 

  • Sobue K, Muramoto Y, Fujita M, Kakiuchi S (1981a) Calmodulin-binding protein from chicken gizzard that interacts with F-actin. Biochem Int 2: 469–476

    CAS  Google Scholar 

  • Sobue K, Muramoto Y, Fujita M, Kakiuchi S (1981b) Purification of a calmodulin-binding protein from chicken gizzard that interacts with F-actin. Proc Natl Acad Sci USA 78: 5652–5655

    Article  PubMed  CAS  Google Scholar 

  • Sobue K, Fujita M, Muramoto U, Kakiuchi S (1981c) The calmodulin-binding protein in micro-tubules is TAU factor. FEBS Lett 132: 137–140

    Article  PubMed  CAS  Google Scholar 

  • Sobue K, Muramoto Y, Fujita M, Kakiuchi S (1981d) Calmodulin-binding protein of erythrocyte cytoskeleton. Biochem Biophys Res Commun 100: 1063–1070

    Article  PubMed  CAS  Google Scholar 

  • Sobue K, Morimoto K, Kanda K, Maruyama K, Kakiuchi S (1982a) Reconstitution of Ca2+-sensitive gelation of actin filaments with filamin, caldesmon and calmodulin. FEBS Lett 138: 289–292

    Article  PubMed  CAS  Google Scholar 

  • Sobue K, Morimoto K, Kanda K, Fukunaga K, Miyamoto E, Kakiuchi S (1982b) Interaction of 135000-M, calmodulin-binding protein (myosin kinase) and F-actin: another Cat+- and calmodulin-dependent flip-flop switch. Biochem Int 5: 503–510

    CAS  Google Scholar 

  • Sobue K, Kanda K, Yamagami K, Kakiuchi S (1982c) Ca2+- and calmodulin-dependent phosphorylation of calspectin (spectrin-like calmodulin-binding protein; fodrin) by protein kinase system in synaptosomal cytosol and membranes. Biomed Res 3: 561–570

    CAS  Google Scholar 

  • Sobue K, Kanda K, Kakiuchi S (1982d) Solubilization and partial purification of protein kinase systems from brain membranes that phosphorylate calspectin, a spectrin-like calmodulinbinding protein (fodrin). FEBS Lett 150: 185–190

    Article  PubMed  CAS  Google Scholar 

  • Sobue K, Kanda K, Adachi J, Kakiuchi S (1983) Calmodulin-binding protein that interact with actin filaments in a Ca2+-dependent flip-flop manner: survery in brain and secretory tissues. Proc Natl Acad Sci USA 80: 6868–6871

    Article  PubMed  CAS  Google Scholar 

  • Steck TL (1974) The organization of proteins in the human red blood cell membrane. J Cell Biol 62: 1–19

    Article  PubMed  CAS  Google Scholar 

  • Stull JT, Silver PJ, Miller JR, Blumenthal DK, Botterman BR, Klug GA (1983) Phosphorylation of myosin light chain in skeletal and smooth muscles. Fed Proc 42: 21–26

    PubMed  CAS  Google Scholar 

  • Teshima Y, Kakiuchi S (1978) Membrane-bound forms of Ca2+-dependent protein modulator: Ca2+-dependent and independent bindings of modulator protein to the particulate fraction from brain. J Cyclic Nucleotide Res 4: 219–231

    PubMed  CAS  Google Scholar 

  • Timasheff SN, Grisham LM (1980) In vitro assembly of cytoplasmic microtubules. Annu Rev Biochem 49: 565–591

    Article  PubMed  CAS  Google Scholar 

  • Tsukita S, Tsukita S, Ishikawa H, Kurokawa M, Morimoto K, Sobue K, Kakiuchi S (1983) Binding sites of calmodulin and actin on the brain spectrin, calspectin. J Cell Biol 97: 574–578

    Article  PubMed  CAS  Google Scholar 

  • Walsh MP, Bridenbaugh R, Glenn W, Kerrick L, Hartshorne DJ (1983) Gizzard Ca2+-independent myosin light chain kinase: evidence in favor of the phosphorylation theory. Fed Proc 42: 45–50

    PubMed  CAS  Google Scholar 

  • Weisenberg RC (1972) Microtubule formation in vitro in solutions containing low calcium concentrations. Science (Wash DC) 177: 1104–1105

    Article  CAS  Google Scholar 

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Kakiuchi, S. (1985). Biochemistry of the Ca2+- and Calmodulin-Dependent Regulation of the Cytoskeleton. In: Marmé, D. (eds) Calcium and Cell Physiology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-70070-5_11

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  • DOI: https://doi.org/10.1007/978-3-642-70070-5_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-70072-9

  • Online ISBN: 978-3-642-70070-5

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