European Biophysics Journal

, 35:40 | Cite as

Transitions in microtubule C-termini conformations as a possible dendritic signaling phenomenon



We model the dynamical states of the C-termini of tubulin dimers that comprise neuronal microtubules. We use molecular dynamics and other computational tools to explore the time-dependent behavior of conformational states of a C-terminus of tubulin within a microtubule and assume that each C-terminus interacts via screened Coulomb forces with the surface of a tubulin dimer, with neighboring C-termini and also with any adjacent microtubule-associated protein 2 (MAP2). Each C-terminus can either bind to the tubulin surface via one of the several positively charged regions or can be allowed to explore the space available in the solution surrounding the dimer. We find that the preferential orientation of each C-terminus is away from the tubulin surface but binding to the surface may also take place, albeit at a lower probability. The results of our model suggest that perturbations generated by the C-termini interactions with counterions surrounding a MAP2 may propagate over distances greater than those between adjacent microtubules. Thus, the MAP2 structure is able to act as a kind of biological wire (or a cable) transmitting local electrostatic perturbations resulting in ionic concentration gradients from one microtubule to another. We briefly discuss the implications the current dynamic modeling may have on synaptic activation and potentiation.


Neuron Synapse MAP Ionic wave Protein filament Electrostatic interaction 



This research was supported by grants from NSERC, MITACS-MMPD and the YeTaDel Foundation. We thank Mr. Eric Carpenter for assistance in computational work. Discussions with Dr. Dan Sackett of NIH are gratefully acknowledged.


  1. Al-Bassam J, Ozer RS, Safer D, Halpain S, Milligan RA (2002) MAP2 and tau bind longitudinally along the outer ridges of microtubule protofilaments. J Cell Biol 157:1187–1196CrossRefPubMedGoogle Scholar
  2. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular biology of the cell. Garland Science Publishing, New YorkGoogle Scholar
  3. Brown JA, Tuszynski JA (1999) A review of the ferroelectric model of microtubules. Ferroelectrics 220:141–155CrossRefGoogle Scholar
  4. Daune M (1999) Molecular biophysics: structures in motion. Oxford University Press, OxfordGoogle Scholar
  5. Khuchua Z, Wozniak DF, Bardgett ME, Yue Z, McDonald M, Boero J, Hartman RE, Sims H, Strauss AW (2003) Deletion of the N-terminus of murine MAP2 by gene targeting disrupts hippocampal CA1 neuron architecture and alters contextual memory. Neuroscience 119:101–111CrossRefPubMedGoogle Scholar
  6. Kiebler MA, DesGroseillers L (2000) Molecular insights into mRNA transport and local translation in the mammalian nervous system. Neuron 25:19–28CrossRefPubMedGoogle Scholar
  7. Kim CH, Lisman JE (2001) A labile component of AMPA receptor-mediated synaptic transmission is dependent on microtubule motors, actin, and N-ethylmaleimide-sensitive factor. J Neurosci 21:4188–4194PubMedGoogle Scholar
  8. Koradi R, Billeter M, Wuthrich K (1996) MolMol: a program for display and analysis of macromolecular structures. J Mol Graph 14:51–55, 29–32Google Scholar
  9. Löwe J, Li H, Downing KH, Nogales E (2001) Refined structure of αβ-tubulin at 3.5 Å. J Mol Biol 313:1083–1095CrossRefGoogle Scholar
  10. Lu Q, Moore GD, Walss C, Luduena RF (1998) Structural and functional properties of tubulin isotypes. Adv Struct Biol 5:203–227CrossRefGoogle Scholar
  11. Makrides V, Shen TE, Bhatia R, Smith BL, Thimm J, Lal R, Feinstein SC (2003) Microtubule-dependent oligomerization of tau: implications for physiological tau function and tauopathies. J Biol Chem 278:33298–33304CrossRefPubMedGoogle Scholar
  12. Mallik B, Masunov A, Lazaridis T (2002) Distance and exposure dependent effective dielectric function. J Comp Chem 23:1090–1099CrossRefGoogle Scholar
  13. Manning G (1978) The molecular theory of polyelectrolyte solutions with applications to the electrostatic properties of polynucleotides. Q Rev Biophys 2:179–246Google Scholar
  14. Nogales E, Wolf SG, Downing KH (1998) Structure of the αβ tubulin dimer by electron crystallography. Nature 391:199–203CrossRefPubMedADSGoogle Scholar
  15. Pedrotti B, Colombo R, Islam K (1994) Interactions of microtubule-associated protein MAP2 with unpolymerized and polymerized tubulin and actin using a 96-well microtiter plate solid-phase immunoassay. Biochemistry 33:8798–8806CrossRefPubMedGoogle Scholar
  16. Ripoll C, Norris V, Thellier M (2004) Ion condensation and signal transduction. Bioessays 26:549–557CrossRefPubMedGoogle Scholar
  17. Sackett DL (1995) Structure and function in the tubulin dimer and the role of the acid carboxyl terminus. In: Biswas BB, Roy S (eds) Subcellular biochemistry–proteins: structure, function and engineering. Kluwer, Dordrecht, 24:255–302Google Scholar
  18. Steward O, Schuman EM (2001) Protein synthesis at synaptic sites on dendrites. Annu Rev Neurosci 24:299–325CrossRefPubMedGoogle Scholar
  19. Stracke R, Bohm KJ, Wollweber L, Tuszynski JA, Unger E (2002) Analysis of the migration behaviour of single microtubules in electric fields. Biochem Biophys Res Commun 293:602–609CrossRefPubMedGoogle Scholar
  20. Swope WC, Andersen HC, Berens PH, Wilson KR (1982) A computer simulation method for the calculation of equilibrium constants for the formation of physical clusters of molecules: application to small water clusters. J Chem Phys 76:637–649CrossRefADSGoogle Scholar
  21. Thorn KS, Ubersax JA, Vale RD (2000) Engineering the processive run length of the kinesin motor. J Cell Biol 151:1093–1100CrossRefPubMedGoogle Scholar
  22. Tokuraku K, Katsuki M, Matui T, Kuroya T, Kotani S (1999) Microtubule-binding property of microtubule-associated protein 2 differs from that of microtubule-associated protein 4 and tau. Eur J Biochem 264:996–1001CrossRefPubMedGoogle Scholar
  23. Wang Z, Sheetz MP (2000) The C-terminus of tubulin increases cytoplasmic dynein and kinesin processivity. Biophys J 78:1955–1964PubMedCrossRefGoogle Scholar
  24. Wong RW, Setou M, Teng J, Takei Y, Hirokawa N (2002) Overexpression of motor protein KIF17 enhances spatial and working memory in transgenic mice. Proc Natl Acad Sci USA 99:14500–14505CrossRefPubMedADSGoogle Scholar
  25. Woolf NJ, Zinnerman MD, Johnson GVW (1999) Hippocampal microtubule-associated protein-2 alterations with contextual memory. Brain Res 821:241–249CrossRefPubMedGoogle Scholar

Copyright information

© EBSA 2005

Authors and Affiliations

  • Avner Priel
    • 1
  • Jack A. Tuszynski
    • 1
  • Nancy J. Woolf
    • 2
  1. 1.Department of PhysicsUniversity of Alberta Edmonton Canada
  2. 2.Behavioral Neuroscience, Department of PsychologyUniversity of CaliforniaLos AngelesUSA

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