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Nonmuscle α-Actinin is an EF-Hand Protein

  • Chapter
Novel Calcium-Binding Proteins

Abstract

In 1965, Ebashi and Ebashi isolated an F-actin crosslinking protein from muscle cells which they called α-actinin. In addition to actin, myosin and tropomyosin it was the fourth component so far found in muscle cells. Immunofluorescence studies on striated muscle showed that α-actinin is localized in the Z-lines which separate the sarcomers and anchor the actin filaments. Therefore, a role for α-actinin in linking actin filaments to the Z-line has been discussed. It is generally assumed that α-actinin strengthens the structure and helps the sarcomeric unit to withstand the force generated by the actin-myosin contraction. Whether the in vitro-enhanced Mg-ATPase activity of actomyosin in the presence of α-actinin (Maruyama and Ebashi 1965) plays a significant role in vivo is not clear. Ten years later Lazarides and Burridge (1975) identified α-actinin also in nonmuscle cells. Like muscle α-actinin, its main activity in vitro is the gelation of an F-actin solution by cross linking actin filaments under certain conditions. The finding that α-actinin can be incorporated into artificial membranes and could form trimeric complexes with actin in the presence of diacylglycerol and palmitic acid (Burn et al. 1985) makes it conceivable that α-actinin might anchor actin filaments to the plasma membrane of nonmuscle cells. Since then several isoforms of α-actinin have been isolated from skeletal and smooth muscle (Feramisco and Burridge 1980; Endo and Masaki 1984) or from vertebrate nonmuscle cells like brain (Duhaiman and Bamburg 1984), macrophages (Bennett et al. 1984), platelets (Landon et al. 1985) and fibroblasts (Burridge and Feramisco 1981).

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References

  • André E, Lottspeich F, Schleicher M, Noegel A (1988) Severin, gelsolin and villin share a homologous sequence in regions presumed to contain F-actin severing domains. J Biol Chem 263:722–727.

    PubMed  Google Scholar 

  • André E, Brink M, Gerisch G, Isenberg G, Noegel A, Schleicher M, Segall JE, Wallraff E (1989) A Dictyostelium mutant deficient in severin, an F-actin fragmenting protein, shows normal motility and chemotaxis. J Cell Biol 108:985–995.

    Article  PubMed  Google Scholar 

  • Arimura C, Suzuki T, Yanagisawa M, Immamura M, Hamada Y, Masaki T (1988) Primary structure of chicken skeletal muscle and fibroblast α-actinin deduced from cDNA sequences. Eur J Biochem 177:649–655.

    Article  PubMed  CAS  Google Scholar 

  • Baron MD, Davison MD, Jones P, Critchley DR (1987) The sequence of chick α-actinin reveals homologies to spectrin and calmodulin. J Biol Chem 262:17623–17629.

    PubMed  CAS  Google Scholar 

  • Bennet H, Condeelis J (1988) Isolation of an immunoreactive analogue of brain fodrin that is associated with the cell cortex of Dictyostelium amoebae. Cell Motil Cytoskeleton 11:303–317.

    Article  Google Scholar 

  • Bennett JP, Zaner KS, Stossel TP (1984) Isolation and some properties of macrophage a-actinin: evidence that it is not an actin gelling protein. Biochemistry 23:5081–5086.

    Article  PubMed  CAS  Google Scholar 

  • Berchtold MW, Epstein P, Beaudet AL, Payne ME, Heizmann CW, Means AR (1987) Structural organization and chromosomal assignment of the parvalbumin gene. J Biol Chem 262:8696–8701.

    PubMed  CAS  Google Scholar 

  • Bray D, Vasiliev J (1989) Networks from mutants. Nature 338:203–204.

    Article  PubMed  CAS  Google Scholar 

  • Brink M, Gerisch G, Isenberg G, Noegel AA, Segall JE, Wallraff E, Schleicher M (1990) A Dictyostelium mutant lacking an F-actin crosslinking protein, the 120 kD gelation factor. J Cell Biol (in press).

    Google Scholar 

  • Brown S, Yamamoto K, Spudich JA (1982) A 40.000 dalton protein from Dictyostelium discoideum affects assembly properties of actin in a Ca2+-dependent manner. J Cell Biol 93:205–210.

    Article  PubMed  CAS  Google Scholar 

  • Burn P, Rotman A, Mayer RK, Burger MM (1985) Diacylglycerol in large α-actinin/actin complexes in the cytoskeleton of activated platelets. Nature 314:469–472.

    Article  PubMed  CAS  Google Scholar 

  • Burridge K, Feramisco JR (1981) Non-muscle α-actinins are calcium sensitive actin binding proteins. Nature 294:565–567.

    Article  PubMed  CAS  Google Scholar 

  • Byers TJ, Husain-Chishti A, Dubreuil RR, Branton D, Goldstein LSB (1989) Sequence similarity of the amino-terminal domain of Drosophila beta-spectrin to α-actinin and dystrophin. J Cell Biol 109:1633–1641.

    Article  PubMed  CAS  Google Scholar 

  • Condeelis J, Vahey M (1982) A calcium and pH-regulated protein from Dictyostelium discoideum that cross-links actin filaments. J Cell Biol 94:466–471.

    Article  PubMed  CAS  Google Scholar 

  • Cross RA, Stewart M, Kendrick-Jones J (1990) Structural predictions for the central domain of dystrophin. FEBS Lett 262:87–92.

    Article  PubMed  CAS  Google Scholar 

  • DeLozanne A, Spudich JA (1987) Disruption of the Dictyostelium myosin heavy chain gene by homologous recombination. Science 236:1086–1091.

    Article  CAS  Google Scholar 

  • Demma M, Warren V, Hock R, Dharmawardhane S, Condeelis J (1990) Isolation of an abundant 50.000-dalton actin filament bundling protein from Dictyostelium amoebae. J Biol Chem 265:2286–2291.

    PubMed  CAS  Google Scholar 

  • Dubreuil RR, Byers TJ, Sillman AL, Bar-Zvi D, Goldstein LSB, Branton D (1989) The complete sequence of Drosophila alpha-spectrin: Conservation of structural domains between alpha-spectrin and alpha-actinin. J Cell Biol 109:2197–2205.

    Article  PubMed  CAS  Google Scholar 

  • Duhaiman AS, Bamburg JR (1984) Isolation of brain α-actinin. Its characterization and comparison of its properties with those of muscle α-actinins. Biochemistry 23:1600–1608.

    Article  PubMed  CAS  Google Scholar 

  • Ebashi S, Ebashi F (1965) α-Actinin, a new structural protein from striated muscle. J Biochem 58:7–12.

    PubMed  CAS  Google Scholar 

  • Eichinger L, Noegel AA, Schleicher M (1990) Domain structure in actin-binding proteins: Expression and functional characterization of truncated severin. (submitted).

    Google Scholar 

  • Einberger H, Mertz R, Hofschneider PH, Neubert WJ (1990) Purification, renaturation and reconstituted protein kinase activity of the Sendai virus large (L) protein: L protein phosphorylates the NP and P proteins in vitro. J Virol (in press).

    Google Scholar 

  • Endo T, Masaki T (1984) Molecular properties and functions in vitro of chicken smooth muscle α-actinin in comparison with those of striated muscle α-actinins. J Biochem 92:1457–1468.

    Google Scholar 

  • Fechheimer M (1987) The Dictyostelium discoideum 30.000-dalton protein is an actin filament-bundling protein that is selectively present in filopodia. J Cell Biol 104:1539–1551.

    Article  PubMed  CAS  Google Scholar 

  • Fechheimer M, Brier J, Rockwell M, Luna EJ, Taylor DL (1982) A calcium and pH-regulated actin binding protein from D. discoideum. Cell Motil 2:287–308.

    Article  CAS  Google Scholar 

  • Feramisco JR, Burridge K (1980) A rapid purification of α-actinin, filamin and 130000 dalton protein from smooth muscle. J. Biol. Chem 225:1194–1199.

    Google Scholar 

  • Garnier J, Osguthorpe DJ, Robson B (1978) Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol 120:97–120.

    Article  PubMed  CAS  Google Scholar 

  • Gorlin JB, Yamin R, Egan S, Stewart M, Stossel TP, Kwiatkowski DJ, Hartwig JH (1990) Human endothelial actin-binding protein (ABP, nonmuscle filamin): A molecular leaf spring. (submitted).

    Google Scholar 

  • Hammonds RG (1987) Protein sequence of DMD gene is related to actin binding domain of α-actinin. Cell 51:1.

    Article  PubMed  CAS  Google Scholar 

  • Hartmann H, Noegel AA, Eckerskorn C, Rapp S, Schleicher M (1989) Ca2+-independent F-actin capping proteins: Cap 32/34, a capping protein from Dictyostelium discoideum, does not share sequence homologies with known actin-binding proteins. J Biol Chem 264:12639–12647.

    PubMed  CAS  Google Scholar 

  • Herzberg O, James MNG (1985) Structure of the calcium regulatory muscle protein troponin C at 2.8 Å resolution. Nature 313:653–659.

    Article  PubMed  CAS  Google Scholar 

  • Hock RS, Condeelis JS (1987) Isolation of a 240-kilodalton actin-binding protein from Dictyostelium discoideum. J Biol Chem 262:394–400.

    PubMed  CAS  Google Scholar 

  • Imamura M, Endo T, Kuroda M, Tanaka T, Masaki T (1988) Substructure and higher structure of chicken smooth muscle α-actinin molecule. J Biol Chem 263:7800–7805.

    PubMed  CAS  Google Scholar 

  • Knecht DA, Loomis WF (1987) Antisense RNA inactivation of myosin heavy chain gene expression in Dictyostelium discoideum. Science 236:1081–1086.

    Article  PubMed  CAS  Google Scholar 

  • Koenig M, Monaco AP, Kunkel LM (1988) The complete sequence of dystrophin predicts a rodshaped cytoskeletal protein. Cell 53:219–228.

    Article  PubMed  CAS  Google Scholar 

  • Korn ED, Hammer III JA (1988) Myosins of nonmuscle cells. Ann Rev Biophys Chem 17:23–45.

    Article  CAS  Google Scholar 

  • Kretsinger RH (1980) Structure and evolution of calcium modulated proteins. CRC Crit Rev Biochem 8:119–174.

    Article  PubMed  CAS  Google Scholar 

  • Landon F, Gache Y, Touitou H, Olomucki A (1985) Properties of two isoforms of human blood platelet α-actinins. Eur J Biochem 153:231–237.

    Article  PubMed  CAS  Google Scholar 

  • Lazarides E, Burridge K (1975) α-Actinin: immunofluorescent localization of a muscle structural protein in non-muscle cells. Cell 6:289–298.

    Article  PubMed  CAS  Google Scholar 

  • Manstein DJ, Titus MA, DeLozanne A, Spudich JA (1989) Gene replacement in Dictyostelium: generation of myosin null mutants. EMBO J 8:923–932.

    PubMed  CAS  Google Scholar 

  • Maruyama K, Ebashi S (1965) α-Actinin, a new structural protein from striated muscle. J Biochem 58:13–19.

    PubMed  CAS  Google Scholar 

  • Nellen W, Silan C, Firtel R (1984) DNA mediated transformation in Dictyostelium discoideum: Regulated expression of an actin gene fusion. Mol Cell Biol 4:2890–2898.

    PubMed  CAS  Google Scholar 

  • Noegel AA, Witke W (1988) Inactivation of the α-actinin gene in Dictyostelium. Dev Genet 9:531–538.

    Article  PubMed  CAS  Google Scholar 

  • Noegel A, Witke W, Schleicher M (1987) Calcium sensitive non muscle α-actinin contains EF-hand structures and highly conserved regions. FEBS Lett 221:391–396.

    Article  PubMed  CAS  Google Scholar 

  • Noegel AA, Rapp S, Lottspeich F, Schleicher M, Stewart M (1989) The Dictyostelium gelation factor shares a putative actin-binding site with α-actinins and dystrophin and also has a rod domain containing six 100-residue motifs that appear to have a cross-beta conformation. J Cell Biol 109:607–618.

    Article  PubMed  CAS  Google Scholar 

  • Pollard TD (1981) Purification of a calcium-sensitive actin gelation protein from Acanthamoeba. J Biol Chem 256:7666–7670.

    PubMed  CAS  Google Scholar 

  • Pollard TD, Cooper JA (1986) Actin and actin-binding proteins. A critical evaluation of mechanisms and functions. Ann Rev Biochem 55:987–1035.

    Article  PubMed  CAS  Google Scholar 

  • Scheel J, Ziegelbauer K, Kupke T, Humbel BM, Noegel AA, Gerisch G, Schleicher M (1989) Hisactophilin, a histidine-rich actin-binding protein from Dictyostelium discoideum. J Biol Chem 264:2832–2839.

    PubMed  CAS  Google Scholar 

  • Schleicher M, Gerisch G, Isenberg G (1984) New actin binding proteins from Dictyostelium discoideum. EMBO J 3:2095–2100.

    PubMed  CAS  Google Scholar 

  • Schleicher M, Noegel A, Schwarz T, Wallraff E, Brink M, Faix J, Gerisch G, Isenberg G (1988) A Dictyostelium mutant with severe defects in α-actinin: its characterization using cDNA probes and monoclonal antibodies. J Cell Sci 90:59–66.

    PubMed  CAS  Google Scholar 

  • Speicher DW, Marchesi VT (1984) Erythrocyte spectrin is comprised of many homologous triple helical segments. Nature 311:177–180.

    Article  PubMed  CAS  Google Scholar 

  • Stossel TP, Chaponnier C, Ezzel RM, Hartwig JH, Janmey PA, Kwiatkowski DJ, Lind SE, Smith DB, Southwick FS, Yin HL, Zaner KS (1985) Nonmuscle actin-binding proteins. Ann Rev Cell Biol 1:353–402.

    Article  PubMed  CAS  Google Scholar 

  • Tschudi C, Young AS, Ruben L, Patton CL, Richards FF (1985) Calmodulin genes in trypanosomes are tandemly repeated and produce multiple mRNAs with a common 5′ leader sequence. Proc Natl Acad Sci USA 82:3998–4002.

    Article  PubMed  CAS  Google Scholar 

  • van Erd JP, Capony JP, Ferraz C and Pechere JF (1978) The amino-acid sequence of troponin C from frog skeletal muscle. Eur J Biochem 91:231–242.

    Article  Google Scholar 

  • Wallraff E, Schleicher M, Modersitzki M, Rieger D, Isenberg G, Gerisch G (1986) Selection of Dictyostelium mutants defective in cytoskeletal proteins: Use of an antibody that binds to the ends of α-actinin rods. EMBO J 5:61–65.

    PubMed  CAS  Google Scholar 

  • Wasenius V-M, Saraste M, Salven P, Eramaa M, Holm L, Lehto V-P (1989) Primary structure of the brain α-spectrin. J Cell Biol 108:79–93.

    Article  PubMed  CAS  Google Scholar 

  • Witke W, Noegel AA (1990) A single base exchange in an intron of the Dictyostelium discoideum α-actinin gene inhibits correct splicing of the RNA but allows transport to the cytoplasm and translation. J Biol Chem 265:34–39.

    PubMed  CAS  Google Scholar 

  • Witke W, Schleicher M, Lottspeich F, Noegel A (1986) Studies on transcription, translation, and structure of α-actinin in Dictyostelium discoideum. J Cell Biol 103:969–975.

    Article  PubMed  CAS  Google Scholar 

  • Witke W, Nellen W, Noegel A (1987) Homologous recombination in the Dictyostelium α-actinin gene leads to an altered mRNA and lack of the protein. EMBO J 6:4143–4148.

    PubMed  CAS  Google Scholar 

  • Witke W, Gurniak CB, Humbel BM, Einberger H, Neubert J, Noegel AA, Schleicher M Expression of an α-actinin fragment in Dictyostelium that carries an actin-binding site. (submitted).

    Google Scholar 

  • Wuestehube LJ, Luna EJ (1987) F-Actin binds to the cytoplasmic surface of ponticulin, a 17 kD integral glycoprotein from Dictyostelium discoideum. J Cell Biol 105:1741–1751.

    Article  PubMed  CAS  Google Scholar 

  • Yin HL, Janmey PA, Schleicher M (1990) Severin is a gelsolin prototype. FEBS Lett 264:78–80.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Walter Witke
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  2. Angelika A. Noegel
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  3. Michael Schleicher
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Editors and Affiliations

  1. Department of Pediatrics Division of Clinical Chemistry, University of Zürich, Steinwiesstraße 75, CH-8032, Zürich, Switzerland

    Claus W. Heizmann

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© 1991 Springer-Verlag Berlin Heidelberg

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Witke, W., Noegel, A.A., Schleicher, M. (1991). Nonmuscle α-Actinin is an EF-Hand Protein. In: Heizmann, C.W. (eds) Novel Calcium-Binding Proteins. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76150-8_18

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  • DOI: https://doi.org/10.1007/978-3-642-76150-8_18

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