Protein Linguistics and the Modular Code of the Cytoskeleton

  • Mario Gimona
Part of the Biosemiotics book series (BSEM, volume 1)

Protein assembly follows linguistic rules, and the combination of linguistic analysis and the use of modular units as building blocks are now beginning to allow first insights into the underlying parameters for the evolution of multidomain proteins. Filaments of the cytoskeleton systems, themselves assembled from modular protein units, display the hallmarks of self-replicating von Neumann automata. The actin cytoskeleton is a prototype for a molecular code that is generated by the assembly of identical subunits, and cells are able to respond to changes in the state of the cytoskeleton. Thus, cytoskeleton assembly generates signs whose purpose is to provide the necessary asymmetry for molecular interactions and that makes organic meaning accessible. The cytoskeleton acts as a code maker, and functions as an internalized, shared background knowledge of a historically evolved linguistic community. It is a modular, universal, and dynamic structure that employs adapters to interact with intracellular and extracellular entities, and it is a molecular machine that engages in biosemiosis via a continuous assembly and disassembly cycle. In this chapter I will discuss how the rules and parameters of protein linguistic assembly, and in particular the cytoskeleton code, reveal a cellular biosemiotic mechanism at work.


Intermediate Filament Curr Opin Cell Biol Linguistic Community Universal Grammar Modular Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Aasland R et al. (2002) Normalization of nomenclature for peptide motifs as ligands of modular protein domains. FEBS Lett 513:141–144.CrossRefPubMedGoogle Scholar
  2. 2.
    Baker MC (2001) The Atoms of Language. Basic Books.Google Scholar
  3. 3.
    Baldassarre M, Ayala I, Beznoussenko G, Giacchetti G, Machesky, LM, Luini A, Buccione R (2006) Actin dynamics at sites of extracellular matrix degradation. Eur J Cell Biol 85:1217–1231.CrossRefPubMedGoogle Scholar
  4. 4.
    Baluska F, Volkmann D, Barlow PW (2004) Eukaryotic cells and their cell bodies: cell theory revised. Ann Bot 94:9–32.CrossRefPubMedGoogle Scholar
  5. 5.
    Barabasi A-L, Oltvai ZN (2004) Network Biology: understanding the cell’s functional organization. Nature Rev Genetics 5:101–113.CrossRefGoogle Scholar
  6. 6.
    Barbieri M (1981) The ribotype theory of the origin of life. J Theor Biol 91:545–601.CrossRefPubMedGoogle Scholar
  7. 7.
    Barbieri M (2003) The organic codes: an introduction to semantic biology. Cambridge University Press, Cambridge.Google Scholar
  8. 8.
    Barbieri M (2005) Life is artifact making. J Biosemiotics 1:107–134.Google Scholar
  9. 9.
    Bayley PM, Martin SR (1991) Microtubule dynamic instability: some possible physical mechanisms and their implications. Biochem Soc Trans 19:1023–1028.PubMedGoogle Scholar
  10. 10.
    Benner SA, Gaucher EA (2001) Evolution, language and analogy in functional genomics. Trends Gene 17:414–418.CrossRefGoogle Scholar
  11. 11.
    Benner SA, Sismour M (2005) Synthetic biology. Nature Rev Genetics 6:533–543.CrossRefGoogle Scholar
  12. 12.
    Bogusky MS (1999) Biosequence exegesis. Science 286:453–455.CrossRefGoogle Scholar
  13. 13.
    Botstein D, Cherry JM (1997) Molecular Linguistics: extracting information from gene and protein sequences. Proc Natl Acad Sci USA 94:5506–5507.CrossRefPubMedGoogle Scholar
  14. 14.
    Brendel V, Busse HG (1984) Genome structure described by formal languages. Nucleic Acid Res 12:2561–2568.CrossRefPubMedGoogle Scholar
  15. 15.
    Brendel V, Beckman JS, Trifonov EN (1986) Linguistics of nucleotide sequences: morphology and comparison of vocabularies. J Biomol Struct Dyn 4:11–21.PubMedGoogle Scholar
  16. 16.
    Brenner SL, Korn ED (1983) On the mechanism of actin monomer-polymer subunit exchange at steady state. J Biol Chem 258:5013–5020.PubMedGoogle Scholar
  17. 17.
    Carlier MF (1991) Nucleotide hydrolysis in cytoskeletal assembly. Curr Opin Cell Biol 3:12–17.CrossRefPubMedGoogle Scholar
  18. 18.
    Chomsky N (1964) The logical basis of linguistic theory. In: Proceedings of the 9th International Congress of Linguistics, Cambridge, Massachusetts/The Hague, pp. 914–978.Google Scholar
  19. 19.
    Chomsky N (2005) Universals of human nature. Psychother Psychosom 74:263–268.CrossRefPubMedGoogle Scholar
  20. 20.
    Doerfler W (1982) In search of more complex genetic codes – can linguistics be a guide? Med. Hypotheses 9:563–579.CrossRefPubMedGoogle Scholar
  21. 21.
    (2002) Editorial Folding as grammar. Nature Struct Biol 9:713.Google Scholar
  22. 22.
    Eigen M, Winkler R (1975) Das Spiel - Naturgesetze steuern den Zufall. Piper Verlag Muenchen.Google Scholar
  23. 23.
    Eriksson HP (2001) Evolution in bacteria. Nature 413:30–31.CrossRefGoogle Scholar
  24. 24.
    Favareau D (2006) The evolutionary history of biosemiotics. In: Barbieri M (ed.) Introduction to biosemiotics. Springer life sciences. ISBN:978-1-4020-4813-5.Google Scholar
  25. 25.
    Fitch WT, Hauser MD, Chomsky N (2005) The evolution of the language faculty: clarifications and implications. Cognition 97:179–210.CrossRefPubMedGoogle Scholar
  26. 26.
    Frischknecht F, Way M (2001) Surfing pathogens and the lessons learned for actin polymerization. Trends Cell Biol 11:30–38.CrossRefPubMedGoogle Scholar
  27. 27.
    Galzitskaya OV, Melnik BS (2003) Prediction of protein domain boundaries from sequence alone. Prot Sci 12:696–701.CrossRefGoogle Scholar
  28. 28.
    Ganapathiraju M, Manoharan V, Klein-Seetharaman J (2004) BLMT: statistical sequence analysis using N-grams. Applied Bioinformatics 3:193–200.CrossRefPubMedGoogle Scholar
  29. 29.
    Gimona M (2006) Protein linguistics – a grammar for modular protein assembly? Nature Rev Mol Cell Biol 7:68–73.CrossRefGoogle Scholar
  30. 30.
    Gitai Z (2005) The new bacterial cell biology: moving parts and subcellular architecture. Cell 120:577–586.CrossRefPubMedGoogle Scholar
  31. 31.
    Goffin JM, Pittet P, Csucs G, Lussi JW, Meister JJ, Hinz B (2006) Focal adhesion size controls tension-dependent recruitment of alpha-smooth muscle actin to stress fibers. J Cell Biol 172:259–268.CrossRefPubMedGoogle Scholar
  32. 32.
    Gourlay CW, Ayscough KR (2005) The actin cytoskeleton: a key regulator of apoptosis and ageing? Nature Rev Mol Cell Biol 6:583–589.CrossRefGoogle Scholar
  33. 33.
    Gourlay CW, Carpp LN, Timpson P, Winder SJ, Ayscough KR (2004) A role for the actin cytoskeleton in cell death and aging in yeast. J Cell Biol 164:803–809.CrossRefPubMedGoogle Scholar
  34. 34.
    Greber UF, Way M (2006) A superhighway to virus infection. Cell 124:741–754.CrossRefPubMedGoogle Scholar
  35. 35.
    Han J-D et al. (2004) Evidence for dynamically organized modularity in the yeast protein-protein interaction network. Nature 430:88–93.CrossRefPubMedGoogle Scholar
  36. 36.
    Hartwell LH, Hopfield JJ, Leibler S, Murray AW (1999) From molecular to modular cell biology. Nature 402:C47–C52.CrossRefPubMedGoogle Scholar
  37. 37.
    Hauser MD, Chomsky N, Fitch WT (2002) The faculty of language: what is it, who has it, and how did it evolve? Science 298:1569–1579.CrossRefPubMedGoogle Scholar
  38. 38.
    Herrmann H, Foisner R (2003) Intermediate filaments: novel assembly models and exciting new functions for nuclear lamins. Cell Mol Life Sci 60:1607–1612.CrossRefPubMedGoogle Scholar
  39. 39.
    Herrmann H, Aebi U (2004) Intermediate filaments: molecular structure, assembly mechanism, and integration into functionally distinct intracellular Scaffolds. Annu Rev Biochem 73:749–89.CrossRefPubMedGoogle Scholar
  40. 40.
    Huang S, Chen L, Libina N, Janes J, Martin GM, Campisi J, Oshima J (2005) Correction of cellular phenotypes of Hutchinson-Gilford Progeria cells by RNA interference. Hum Genet 118:444–450.CrossRefPubMedGoogle Scholar
  41. 41.
    Huynen MA, Snel B, Mering C, Bork P (2003) Function prediction and protein networks. Curr Opin Cell Biol 15:191–198.CrossRefPubMedGoogle Scholar
  42. 42.
    Ji S (1997) Isomorphism between cell and human languages: molecular biological, bioinformatic and linguistic implications. Biosynthesis 44:17–39.Google Scholar
  43. 43.
    Ji S, Ciobanu G (2002) Conformon-driven biopolymer shape changes in cell modelling. Biosystems 70:165–181.CrossRefGoogle Scholar
  44. 44.
    Koonin EV, Wolf YI, Karev GP (2002) The structure of the protein universe and genome evolution. Nature 420:218–223.CrossRefPubMedGoogle Scholar
  45. 45.
    Kreplak L, Aebi U, Herrmann H (2004) Molecular mechanisms underlying the assembly of intermediate filaments. Exp Cell Res 301:77–83.CrossRefPubMedGoogle Scholar
  46. 46.
    Loose C, Jensen K, Rigoutsos I, Stephanopoulos (2006) A linguistic model for the rational design of antimicrobial peptides. Nature 443:867–869.CrossRefPubMedGoogle Scholar
  47. 47.
    Mange D, Madon D, Stauffer A, Tempesti G (1997) Von Neumann revisited: a turing machine with self-repair and self-reproduction properties. Robotics Autonom Syst 22:35–58.CrossRefGoogle Scholar
  48. 48.
    Mantegna RN, Buldyrev SV, Goldberger AL, Havlin S, Peng CK, Simons M, Stanley HE (1994) Linguistic features of noncoding DNA sequences. Phys Rev Lett 73:3169–3172.CrossRefPubMedGoogle Scholar
  49. 49.
    Margulies L, Dolan MF, Guerrero R (2000) The chimeric eucaryote: origin of the nucleus from karyomastigont in amitochondriate protists. Proc Natl Acad Sci USA 97:6954–6959.CrossRefGoogle Scholar
  50. 50.
    Mattout A, Dechat T, Adam SA, Goldman RD, Gruenbaum Y (2006) Nuclear lamins, diseases and aging. Curr Opin Cell Biol 18:335–341.CrossRefPubMedGoogle Scholar
  51. 51.
    Moller-Jensen J, Lowe J (2005) Increasing complexity of the bacterial cytoskeleton. Curr Opin Cell Biol 17:75–81.CrossRefPubMedGoogle Scholar
  52. 52.
    Papin JA, Hunter T, Palsson BO, Subramaniam S (2005) Reconstruction of cellular signalling networks and analysis of their properties. Nature Rev Mol Cell Biol 6:99–111.CrossRefGoogle Scholar
  53. 53.
    Park S-H, Zarrinpar A, Lim WA (2003) Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms. Science 299:1061–1064.CrossRefPubMedGoogle Scholar
  54. 54.
    Pawson T (1995) Protein modules and signalling networks. Nature 373:573–580.CrossRefPubMedGoogle Scholar
  55. 55.
    Pawson T (2001) Specificity in signal transduction: from phosphotyrosine-SH2 domain. Trends Genetics 17:414–418.CrossRefGoogle Scholar
  56. 56.
    Pearson H (2006) Codes and enigmas. Nature 444:259–261.CrossRefPubMedGoogle Scholar
  57. 57.
    Pesole G, Attimonelli M, Saccone C (1994) Linguistic approaches to the analysis of sequence information. Trends Biotechnol 12:401–408.CrossRefPubMedGoogle Scholar
  58. 58.
    Ploubidou A, Way M (2001) Viral transport and the cytoskeleton. Curr Opin Cell Biol 13:97–105.CrossRefPubMedGoogle Scholar
  59. 59.
    Pollard TD (2003) The cytoskeleton, cellular motility and the reductionist agenda. Nature 422:741–745.CrossRefPubMedGoogle Scholar
  60. 60.
    Popov O, Segal DM, Trifonov EN (1996) Linguistic complexity of protein sequences as compared to texts of human languages. Biosystems 38:65–74.CrossRefPubMedGoogle Scholar
  61. 61.
    Przytycka T, Aurora R, Rose GD (1999) A protein taxonomy based on secondary structure. Nature Struct Biol 6:672–682.CrossRefPubMedGoogle Scholar
  62. 62.
    Przytycka T, Srinivasan R, Rose GD (2002) Recursive domains in proteins. Prot Sci 11:409–417.CrossRefGoogle Scholar
  63. 63.
    Rivero F, Cvrcková F Origins and Evolution of the Actin Cytoskeleton. In: Gáspár J. (ed.) Origins and Evolution of Eukaryotic Endomembranes and Cytoskeleton. ISBN: 1-58706-204-6.Google Scholar
  64. 64.
    Rottner K, Stradal TE, Wehland J (2005) Bacteria-host-cell interactions at the plasma membrane: stories on actin cytoskeleton subversion. Dev Cell 9:3–17.CrossRefPubMedGoogle Scholar
  65. 65.
    Russ WP, Lowery DM, Mishra P, Yaffe MB, Ranganathan R (2005) Natural-like function in artificial WW domains. Nature 437:579–583.CrossRefPubMedGoogle Scholar
  66. 66.
    Sagolla MS, Dawson SC, Mancuso JJ, Cande WZ (2006) Three-dimensional analysis of mitosis and cytokinesis in the binucleate parasite Giardia intestinalis. J Cell Sci 119:4889–4900.CrossRefPubMedGoogle Scholar
  67. 67.
    Searls DB (2001) Reading the book of life. Bioinformatics. 17:579–580.CrossRefPubMedGoogle Scholar
  68. 68.
    Searls DB (2002) The language of genes. Nature 420:211–217.CrossRefPubMedGoogle Scholar
  69. 69.
    Searls DB (2003) Trees of life and of language. Nature 426:391–392.CrossRefPubMedGoogle Scholar
  70. 70.
    Sheterline P, Handel SE, Molloy C, Hendry KA (1991) The nature and regulation of actin filament turnover in cells. Acta Histochem. Suppl 41:303–309.PubMedGoogle Scholar
  71. 71.
    Shih YL, Rothfield L (2006) The bacterial cytoskeleton. Microbiol Mol Biol Rev 70:729–574.CrossRefPubMedGoogle Scholar
  72. 72.
    Sim J, Kim SY, Lee J (2005) PPRODO: prediction of protein domain boundaries using neural networks. Proteins 59:627–632.CrossRefPubMedGoogle Scholar
  73. 73.
    Socolich M, Lockless SW, Russ WP, Lee H, Gardner KH, Ranganathan R (2005) Evolutionary information for specifying a protein fold. Nature 437:512–518.CrossRefPubMedGoogle Scholar
  74. 74.
    Sonnhammer ELL, Kahn D (1994) Modular arrangement of proteins as inferred from analysis of homology. Protein Sci 3:482–492.PubMedCrossRefGoogle Scholar
  75. 75.
    Steels L, Oudeyer P-Y (2000) The cultural evolution of syntactic constraints in phonology. In: Artificial Life VII: Proceedings of the seventh International Conference on Artificial Life. The MIT Press, Cambridge, Massachusetts, pp. 382–394.Google Scholar
  76. 76.
    Steels L (2000) The puzzle of language evolution. Kognitionswissenschaft 8:143–150.CrossRefGoogle Scholar
  77. 77.
    Sudol M (1998) From src homology modules to other signalling domains: proposal of the ‘Protein Recognition Code’. Oncogene 17:1469–1474.CrossRefPubMedGoogle Scholar
  78. 78.
    Sudol M, Recinos CC, Abraczinskas J, Humbert J, Farooq A (2005) WW or WoW: the WW domains in a union of bliss. IUBMB Life 57:773–778.CrossRefPubMedGoogle Scholar
  79. 79.
    Trifonov EN (2000) Earliest pages in bioinformatics. Bioinformatics 16:5–9.CrossRefPubMedGoogle Scholar
  80. 80.
    Turner BM (2007) Defining an epigenetic code. Nature Cell Biol 9:2–6.CrossRefPubMedGoogle Scholar
  81. 81.
    Tuszynski JA, Trpisova B, Sept D, Sataric MV (1997) The enigma of microtubules and their self-organizing behavior in the cytoskeleton. Biosystems 42:153–175.CrossRefPubMedGoogle Scholar
  82. 82.
    Van Buren V, Cassimeris L, Odde DJ (2005) Mechanochemical model of microtubule structure and self-assembly kinetics. Biophys J 89:2911–2926.CrossRefGoogle Scholar
  83. 83.
    Vendramini D (2005) Noncoding DNA and the teem theory of inheritance, emotions and innate behaviour. Medical Hypotheses 64:512–519.CrossRefPubMedGoogle Scholar
  84. 84.
    Vidal M (2005) Interactome modelling. FEBS Lett 579:1834–1838.CrossRefPubMedGoogle Scholar
  85. 85.
    Werner E (2005) Genome semantics, in silico multicellular systems and the Central Dogma. FEBS Lett 579:1779–1782.CrossRefPubMedGoogle Scholar
  86. 86.
    Witzany G (2006) From Umwelt to Mitwelt: natural laws versus rule-governed sign mediated interactions (rsi’s). Semiotica 158:425–438.CrossRefGoogle Scholar
  87. 87.
    Witzany G (2006) Serial Endosymbiotic Theory (set): the biosemiotic update. Acta Biotheor 54:103–117.CrossRefPubMedGoogle Scholar
  88. 88.
    Wuchty S, Oltvai ZN, Barabasi A-L (2003) Evolutionary conservation of motif constituents in the yeast interaction network. Nature Genetics 35:176–179.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media B.V 2008

Authors and Affiliations

  • Mario Gimona
    • 1
  1. 1.Sud, Department of Cell Biology and OncologyUnit of Actin Cytoskeleton RegulationItaly

Personalised recommendations