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Titin/connectin-related proteins in C. elegans: a review and new findings

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References

  • Bagnato P, Barone V, Giacomello E, Rossi D, Sorrentino V, (2003) Binding of an ankyrin-1 isoform to obscurin suggests a molecular link between the sarcoplasmic reticulum and myofibrils in striated muscles J Cell Biol 160:245–253

    Article  PubMed  CAS  Google Scholar 

  • Bang M-L, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S, (2001) The complete gene sequence of titin, expression of an unusual ~700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system Circ Res 89:1065–1072

    PubMed  CAS  Google Scholar 

  • Barral JM, Bauer CC, Ortiz I, Epstein HF, (1998) unc-45 mutations in C. elegans implicate a CRO1/She4p-like domain in myosin assembly J Cell Biol 143:1215–1225

    Article  PubMed  CAS  Google Scholar 

  • Benian GM, Kiff JE, Neckelmann N, Moerman DG, Waterston RH, (1989) The sequence of twitchin: an unusually large protein implicated in regulation of myosin activity in C. elegans Nature 342:45–50

    Article  PubMed  CAS  Google Scholar 

  • Benian GM, L’Hernault SW, Morris ME, (1993) Additional sequence complexity in the muscle gene, unc-22, and its encoded protein, twitchin, of C. elegans Genetics 134:1097–1104

    PubMed  CAS  Google Scholar 

  • Benian GM, Tinley TL, Tang X, Borodovsky M, (1996) The C. elegans gene unc-89, required for muscle M-line assembly, encodes a giant modular protein composed of Ig and signal transduction domains J Cell Biol 132:835–848

    Article  PubMed  CAS  Google Scholar 

  • Blomberg N, Baraldi E, Sattler M, Saraste M, Nilges M, (2000) Structure of a PH domain from the C. elegans muscle protein UNC-89 suggests a novel function Structure 8:1079–1087

    Article  PubMed  CAS  Google Scholar 

  • Blumenthal T, Steward K, (1997) RNA processing and gene structure In: Riddle D, Blumentha T, Meyer BJ, Priess JR, (eds.). C. elegans II Cold Spring Harbor Laboratory Press New York pp. 117–145

    Google Scholar 

  • Borisov AB, Raeker MO, Kontrogianni-Konstantopoulos A, Yang K, Kurnit DM, Bloch RJ, Russell MW, (2003) Rapid response of cardiac obscurin gene cluster to aortic stenosis: differential activation of Rho-GEF and MLCK and involvement in hypertrophic growth Biochem Biophys Res Commun 310:910–918

    Article  PubMed  CAS  Google Scholar 

  • Champagne MB, Edwards KA, Erickson HP, Kiehart DP, (2000) Drosophila stretchin-MLCK is a novel member of the titin/myosin light chain kinase family J Mol Biol 300:759–777

    Article  PubMed  CAS  Google Scholar 

  • Chen M, Cheng A, Candotti F, Zhou Y-J, Hymel A, Fasth A, Notarangelo LD, O’Shea JJ, (2000) Complex effects of naturally occurring mutations in the JAK3 pseudokinase domain: evidence for interactions between the kinase and pseudokinase domains Mol Cell Biol 20:947–956

    Article  PubMed  CAS  Google Scholar 

  • De Toledo M, Colombo K, Nagase T, Ohara O, Fort P, Blangy A, (2000) The yeast exchange assay, a new complementary method to screen for Dbl-like protein specificity: identification of a novel RhoA exchange factor FEBS Lett 480(2–3):287–292

    Article  PubMed  Google Scholar 

  • Flaherty DB, Gernert KM, Shmeleva N, Tang X, Mercer KB, Borodovsky M, Benian GM, (2002) Titins in C. elegans with unusual features: coiled-coil domains, novel regulation of kinase activity and two new possible elastic regions J Mol Biol 323:533–549

    Article  PubMed  CAS  Google Scholar 

  • Freiburg A, Trombitas K, Hell W, Cazorla O, Fougerousse F, Centner T, Kolmerer B, Witt C, Beckmann JS, Gregorio CC, Granzier H, Labeit S, (2000) Series of exon-skipping events in the elastic spring region of titin as the structural basis of myofibrillar elastic diversity Circ Res 86:1114–1121

    PubMed  CAS  Google Scholar 

  • Fukuzawa A, Shimamura J, Takemori S, Kanzawa N, Yamaguchi M, Sun P, Maruyama K, Kimura S, (2001) Invertebrate connectin spans as much as 3.5 μm in the giant sarcomeres of crayfish claw muscle EMBO J 20:4826–4835

    Article  PubMed  CAS  Google Scholar 

  • Funabara D, Watabe S, Mooers SU, Narayan S, Dudas C, Hartshorne DJ, Siegman MJ, Butler TM, (2003). Twitchin from molluscan catch muscle J Biol Chem 278:29308–29316

    Article  PubMed  CAS  Google Scholar 

  • Gerull B, Gramlich M, Atherton J, McNabb M, Trombitas K, Sasse-Klaassen S, Seidman JG, Seidman C, Granzier H, Labeit S, Frenneaux M, Thierfelder L, (2002) Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy Nat Gen 30:201–204

    Article  CAS  Google Scholar 

  • Granzier H, Labeit S, (2002) Cardiac titin: an adjustable multi-functional spring J Physiol 541.2:335–342

    Article  CAS  Google Scholar 

  • Greaser M, (2001) Identification of new repeating motifs in titin Proteins 43:145–149

    Article  PubMed  CAS  Google Scholar 

  • Gutierrez-Cruz G, Van Heerden A, Wang K, (2001) Modular motif, structural folds and affinity profiles of PEVK segment of human fetal skeletal muscle titin J Biol Chem 276:7442–7449

    Article  PubMed  CAS  Google Scholar 

  • Hackman P, Vihola A, Haravuori H, Marchand S, Sarparanta J, de Seze J, Labeit S, Witt C, Peltonen L, Richard I, Udd B, (2002) Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin Am J Hum Genet 71:492–500

    Article  PubMed  CAS  Google Scholar 

  • Hakeda S, Endo S, Saigo K, (2000) Requirements of kettin, a giant muscle protein highly conserved in overall structure in evolution, for normal muscle function, viability, and flight activity of Drosophila J Cell Biol 148:101–114

    Article  PubMed  CAS  Google Scholar 

  • Heierhorst J, Probst WC, Kohanski RA, Buku A, Weiss KR, (1995) Phosphorylation of myosin regulatory light chains by the molluscan twitchin kinase Eur J Biochem 233:426–431

    Article  PubMed  CAS  Google Scholar 

  • Heierhorst J, Tang X, Lei J, Probst WC, Weiss KR, Kemp BE, Benian GM, (1996) Substrate specificity and inhibitor sensitivity of Ca2+/S100-dependent twitchin kinases Eur J Biochem 242:454–459

    Article  PubMed  CAS  Google Scholar 

  • Hobert O, Moerman DG, Clark KA, Beckerle MC, Ruvkun G, (1999) A conserved LIM protein that affects muscular adherens junction integrity and mechanosensory function in C. elegans J Cell Biol 144:45–57

    Article  PubMed  CAS  Google Scholar 

  • Hsieh C, Fukumoto S, Layne MD, Maemura K, Charles H, Patel A, Perrella MA, Lee M, (2000) Striated muscle preferentially expressed genes α and β are two serine/threonine protein kinases derived from the same gene as the aortic preferentially expressed Gene-1 J Biol Chem 275:36966–36973

    Article  PubMed  CAS  Google Scholar 

  • Hu S-H, Parker MW, Lei J, Wilce MCJ, Benian GM, Kemp BE, (1994) Insights into autoregulation from the crystal structure of twitchin kinase Nature 369:581–584

    Article  PubMed  CAS  Google Scholar 

  • Itoh-Satoh M, Takeharu H, Nishi H, Koga Y, Arimura T, Koyanagi T, Megumi T, Shigeru H, Ueda K, Nouchi T, Hiroe M, Marumo F, Imaizumi T, Yasunami M, Kimura A, (2002) Titin mutations as the molecular basis for dilated cardiomyopathy Biochem Biophys Res Comm 291:385–393

    Article  PubMed  CAS  Google Scholar 

  • Kobe B, Heierhorst J, Feil SC, Parker MW, Benian GM, Weiss KR, Kemp BE, (1996) Giant protein kinases: domain interactions and structural basis of autoregulation EMBO J 15:6810–6821

    PubMed  CAS  Google Scholar 

  • Kolmerer B, Clayton J, Benes V, Allen T, Ferguson C, Leonard K, Weber U, Knekt M, Ansorge W, Labeit S, Bullard B, (2000) Sequence and expression of the kettin gene in Drosophila melanogaster and Caenorhabditis elegans J Mol Biol 296(2):435–448

    Article  PubMed  CAS  Google Scholar 

  • Kontrogianni-Konstantopoulos A, Jones EM, Van Rossum DB, Bloch RJ, (2003) Obscurin is a ligand for small ankyrin 1 in skeletal muscle Mol Biol Cell 14:1138–1148

    Article  PubMed  CAS  Google Scholar 

  • Kontrogianni-Konstantopoulos A, Catino DH, Strong JC, Randall WR, Bloch RJ, (2004) Obscurin regulates the organization of myosin into A-bands Am J Physiol Cell Physiol 287: C209–C217

    Article  PubMed  CAS  Google Scholar 

  • Lei J, Tang X, Chambers TC, Pohl J, Benian GM, (1994) Protein kinase domain of twitchin has protein kinase activity and an autoinhibitory region J Biol Chem 269:21078–21085

    PubMed  CAS  Google Scholar 

  • Linke WA, Granzier H, (1998) A spring tale: new facts on titin elasticity Biophys J 75:2613–2614

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Rost B, (2003) NORSp: predictions of long regions without regular secondary structure Nucl Acids Res 31:3833–3835

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Tan H, Rost B, (2002) Loopy proteins appear conserved in evolution J Mol Biol 322:53–64

    Article  PubMed  CAS  Google Scholar 

  • Mercer KB, Flaherty DB, Miller RK, Qadota H, Tinley TL, Moerman DG, Benian GM, (2003) Caenorhabditis elegans UNC-98, a C2H2 Zn finger protein, is a novel partner of UNC-97/PINCH in muscle adhesion complexes Mol Biol Cell 14:2492–2507

    Article  PubMed  CAS  Google Scholar 

  • Moerman DG, Benian GM, Waterston RH, (1986) Molecular cloning of the muscle gene unc-22 in C. elegans by Tc1 transposon tagging Proc Natl Acad Sci USA 83:2579–2583

    Article  PubMed  CAS  Google Scholar 

  • Moerman DG, Benian GM, Barstead RJ, Schreifer L, Waterston RH, (1988) Identification and intracellular localization of the unc-22 gene product of C. elegans Genes Develop 2:93–105

    PubMed  CAS  Google Scholar 

  • Moerman DG, Fire A, (1997) Muscle: structure, function and development In: Riddle DL, Blumenthal T, Meyer BJ, Priess JR, (eds.) C. elegans II Cold Spring Harbor Laboratory Press Cold Spring Harbor, New York pp. 417–470

    Google Scholar 

  • Probst WC, Cropper EC, Heierhorst J, Hooper SL, Jaffe H, Vilim F, Beushausen S, Kupfermann I, Weiss KR, (1994) cAMP-dependent phosphorylation of Aplysia twitchin may mediate modulation of muscle contractions by neuropeptide cotransmitters Proc Natl Acad Sci USA 91:8487–8491

    Article  PubMed  CAS  Google Scholar 

  • Rogalski TM, Gilbert MM, Devenport D, Norman KR, Moerman DG, (2003) DIM-1, a novel immunoglobulin superfamily protein in C. elegans, is necessary for maintaining body wall muscle integrity Genetics 163:905–915

    PubMed  CAS  Google Scholar 

  • Russell MW, Raeker MO, Korytkowski KA, Sonneman KJ, (2002) Identification, tissue expression and chromosomal localization of human Obscurin-MLCK, a member of the titin and Dbl families of myosin light chain kinases Gene 282:237–246

    Article  PubMed  CAS  Google Scholar 

  • Siegman MJ, Funabara D, Kinoshita S, Watabe S, Hartshorne DJ, Butler TM, (1998) Phosphorylation of a twitchin-related protein controls catch and calcium sensitivity of force production in invertebrate smooth muscle Proc Natl Acad Sci USA 95:5383–5388

    Article  PubMed  CAS  Google Scholar 

  • Small TM, Flaherty DB, Mercer KB, Borodovsky M, Benian GM, (2001) A new isoform of UNC-89 with two MLCK-like protein kinase domains Mol Biol Cell 12:37a

    Google Scholar 

  • Small TM, Flaherty DB, Gernert K, Borodovsky M, Benian GM, (2003) Two new isoforms of UNC-89 (C. elegans obscurin) containing MLCK-like protein kinase domains Mol Biol Cell 14:46a

    Google Scholar 

  • Small TM, Gernert KM, Flaherty DB, Mercer KB, Borodovsky M, Benian GB, (2004) Three new isoforms of C. elegans UNC-89 containing MLCK-like protein kinase domains J Mol Biol 342:91–108

    Article  PubMed  CAS  Google Scholar 

  • Southgate R, Ayme-Southgate A, (2001) Alternative splicing of an amino-terminal PEVK-like region generates multiple isoforms of Drosophila projectin J Mol Biol 313:1035–1043

    Article  PubMed  CAS  Google Scholar 

  • Tabuchi K, Biederer T, Butz S, Sudhof TC, (2002) CASK participates in alternative tripartite complexes in which Mint 1 competes for binding with Caskin 1, a novel CASK-binding protein J Neurosc 22:4264–4273

    CAS  Google Scholar 

  • Teichmann SA, Chothia C, (2000) Immunoglobulin superfamily proteins in Caenorhabditis elegans J Mol Biol 296:1367–1383

    Article  PubMed  CAS  Google Scholar 

  • Tskhovrebova L, Trinick J, (2003) Titin: properties and family relationships Nat Rev Mol Cell Biol 4:679–689

    Article  PubMed  CAS  Google Scholar 

  • Waterston RH, Thomson JN, Brenner S, (1980) Mutants with altered muscle structure in C. elegans Dev Biol 77:271–302

    Article  PubMed  CAS  Google Scholar 

  • Waterston RH, (1988) Muscle In: Wood WB, (ed.). The Nematode Caenorhabditis elegans Cold Spring Harbor Laboratory Press Cold Spring Harbor, New York 281–335

    Google Scholar 

  • Williams BD, Waterston RH, (1994) Genes critical for muscle development and function in C. elegans identified through lethal mutations J Cell Biol 124:475–490

    Article  PubMed  CAS  Google Scholar 

  • Xu X, Meiler SE, Zhong TP, Mohideen M, Crossley DA, Burggren WW, Fishman MC, (2002) Cardiomyopathy in zebrafish due to mutation in an alternatively spliced exon of titin Nat Gen 30:205–209

    CAS  Google Scholar 

  • Young P, Ehler E, Gautel M, (2001) Obscurin, a giant sarcomeric Rho guanine nucleotide exchange factor protein involved in sarcomere assembly J Cell Biol 154:123–136

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank the following individuals for generating and sending to us unc-89 mutant alleles: Gary Moulder and Robert Barstead (Oklahoma Medical Research Foundation) for ok1116, Shohei Mitani (Tokyo Women’s Medical University) for tm752, and Laurent Segalat (University of Lyon) for five cx alleles. We thank Kim Gernert for helping us analyze some new aspects of the twitchin sequences. We are grateful to our lab colleagues, Kristie Mercer and Rachel Miller, for helpful comments and discussion. We also thank the NIH for their financial support (grant no. AR051466).

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  1. Department of Pathology, Emory University, Atlanta, GA, 30322, USA

    Tracey M. Ferrara, Denise B. Flaherty & Guy M. Benian

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  1. Tracey M. Ferrara
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  2. Denise B. Flaherty
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  3. Guy M. Benian
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Correspondence to Guy M. Benian.

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Ferrara, T.M., Flaherty, D.B. & Benian, G.M. Titin/connectin-related proteins in C. elegans: a review and new findings. J Muscle Res Cell Motil 26, 435–447 (2005). https://doi.org/10.1007/s10974-005-9027-4

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