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tba-5  -  Protein TBA-5

Caenorhabditis elegans

 
 
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Disease relevance of tubulin

  • In view of the small difference in drug binding abilities between nematode intestinal and mammalian brain tubulin it still remains unclear whether the selective toxicity of MBZ can be solely explained by its interference with the parasite's microtubular system [1].
  • Expression of cloned beta-tubulin genes of Haemonchus contortus in Escherichia coli: interaction of recombinant beta-tubulin with native tubulin and mebendazole [2].
 

High impact information on tubulin

  • Our results are consistent with the hypothesis that tubulin heterogeneity contributes to the formation of structurally and functionally distinct sets of microtubules [3].
  • MT-affinity-regulating kinases (MARKs) are novel mammalian serine/threonine kinases that phosphorylate the tubulin-binding domain of MAPs and thereby cause their detachment from MTs and increased MT dynamics [4].
  • In fact, C. elegans phb-2(ad2154) was also found to be resistant to numerous other drugs that bind tubulin and to camptothecin, yet this mutant was sensitive to nocodazole and phalloidin [5].
  • In contrast, actin and tubulin mRNA and rRNA are either not present in P granules, or are present at relatively low levels [6].
  • RNAi in green fluorescent protein (GFP)-tagged strains to follow tubulin, PIE-1, and chromatin showed that deficient proteoglycan biosynthesis uncouples the stability of newly formed cell membranes from cytokinesis, whereas cleavage furrow initiation, mitotic spindle function, karyokinesis, and partitioning of intrinsic components are intact [7].
 

Chemical compound and disease context of tubulin

 

Biological context of tubulin

  • This is the first study of posttranslationally modified tubulin in nematode spermatogenesis [9].
  • In all transient tubulin structures described in spermatocytes and spermatids of H. polygyrus, detyrosination, tyrosination, and polyglutamylation were detected, but acetylation and polyglycylation were not [9].
  • These data indicate that C. elegans is a useful model for examining the interactions between microtubule inhibitors and the colchicine binding site of nematode tubulin [10].
  • Studies on the interaction of HSP16-2 with fluorescently-labeled and radiolabeled actin and tubulin reveal that this smHSP possesses a high affinity for unfolded intermediates which form early on the aggregation pathway, but has no apparent substrate specificity [11].
  • Three of the four loss-of-function, missense mutations result in elevated mec-7 message levels, suggesting a defect in tubulin autoregulation that may be attributable to a loss in the ability to form heterodimers [12].
 

Anatomical context of tubulin

 

Associations of tubulin with chemical compounds

  • These results show that the benzimidazole group of anthelmintics interacts specifically with nematode tubulin and that their selectivity, at least in part, is a direct consequence of such interaction [15].
  • In particular, oxfendazole and thiabendazole had virtually no effect on mammalian tubulin assembly whereas they were both good inhibitors of nematode tubulin polymerization [15].
  • Intestinal tubulin as possible target for the chemotherapeutic action of mebendazole in parasitic nematodes [1].
  • The activity of tubulin: tyrosine ligase exhibits a parallel pattern, while arginyltransferase activity has a plateau between L2 and L4 [16].
  • Western blots with anti-tubulin antibody showed that the albendazole resistant strain had an altered tubulin [17].
 

Other interactions of tubulin

  • One of these missense mutations is located within a motif that is common to all presenilins. spe-4 mutants were also examined for other partitioning defects and tubulin was found to accumulate in unusual deposits close to the plasma membrane [18].
  • The dpy-20 marked-mediated suppression of the alpha-1 tubulin gene expression was observed both in the cis and trans configurations [14].
  • Our identification of two recessive, complementing alleles of a beta-tubulin that disrupt nuclear-centrosome centration and rotation in the early embryo originally suggested that this tubulin, tbb-2, has specialized functions [19].
  • We show that structural protein arrays consisting largely of collagen, myosin, and tubulin, and their associated proteins can be imaged in three dimensions with high contrast and resolution by laser-scanning second harmonic generation (SHG) microscopy [20].
  • In this article we characterize, from a structural point of view, all 16 members of the tubulin gene family of Caenorhabditis elegans (9 alpha-tubulins, 6 beta-tubulins, and 1 gamma-tubulin) [21].
 

Analytical, diagnostic and therapeutic context of tubulin

References

  1. Intestinal tubulin as possible target for the chemotherapeutic action of mebendazole in parasitic nematodes. Köhler, P., Bachmann, R. Mol. Biochem. Parasitol. (1981) [Pubmed]
  2. Expression of cloned beta-tubulin genes of Haemonchus contortus in Escherichia coli: interaction of recombinant beta-tubulin with native tubulin and mebendazole. Lubega, G.W., Geary, T.G., Klein, R.D., Prichard, R.K. Mol. Biochem. Parasitol. (1993) [Pubmed]
  3. mec-7 is a beta-tubulin gene required for the production of 15-protofilament microtubules in Caenorhabditis elegans. Savage, C., Hamelin, M., Culotti, J.G., Coulson, A., Albertson, D.G., Chalfie, M. Genes Dev. (1989) [Pubmed]
  4. MAPs, MARKs and microtubule dynamics. Drewes, G., Ebneth, A., Mandelkow, E.M. Trends Biochem. Sci. (1998) [Pubmed]
  5. A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical multidrug resistance. Zubovych, I., Doundoulakis, T., Harran, P.G., Roth, M.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Analysis of RNA associated with P granules in germ cells of C. elegans adults. Schisa, J.A., Pitt, J.N., Priess, J.R. Development (2001) [Pubmed]
  7. The terminal phase of cytokinesis in the Caenorhabditis elegans early embryo requires protein glycosylation. Wang, H., Spang, A., Sullivan, M.A., Hryhorenko, J., Hagen, F.K. Mol. Biol. Cell (2005) [Pubmed]
  8. Binding of [3H]benzimidazole carbamates to mammalian brain tubulin and the mechanism of selective toxicity of the benzimidazole anthelmintics. Russell, G.J., Gill, J.H., Lacey, E. Biochem. Pharmacol. (1992) [Pubmed]
  9. The microtubular system and posttranslationally modified tubulin during spermatogenesis in a parasitic nematode with amoeboid and aflagellate spermatozoa. Mansir, A., Justine, J.L. Mol. Reprod. Dev. (1998) [Pubmed]
  10. Colchicine binding in the free-living nematode Caenorhabditis elegans. Russell, G.J., Lacey, E. Biochim. Biophys. Acta (1989) [Pubmed]
  11. Structure-function studies on small heat shock protein oligomeric assembly and interaction with unfolded polypeptides. Leroux, M.R., Melki, R., Gordon, B., Batelier, G., Candido, E.P. J. Biol. Chem. (1997) [Pubmed]
  12. Mutations in the Caenorhabditis elegans beta-tubulin gene mec-7: effects on microtubule assembly and stability and on tubulin autoregulation. Savage, C., Xue, Y., Mitani, S., Hall, D., Zakhary, R., Chalfie, M. J. Cell. Sci. (1994) [Pubmed]
  13. Characterization and biological activities of anti-Brugia pahangi tubulin monoclonal antibodies. Bughio, N.I., Faubert, G.M., Prichard, R. Int. J. Parasitol. (1993) [Pubmed]
  14. Effect of the dpy-20 and rol-6 cotransformation markers on alpha-tubulin gene expression in C. elegans transformants. Fukushige, T., Siddiqui, S.S. Transgenic Res. (1995) [Pubmed]
  15. A comparison of the interaction of anthelmintic benzimidazoles with tubulin isolated from mammalian tissue and the parasitic nematode Ascaridia galli. Dawson, P.J., Gutteridge, W.E., Gull, K. Biochem. Pharmacol. (1984) [Pubmed]
  16. Activity patterns of aminoacyl-tRNA synthetases, tRNA methylases, arginyltransferase and tubulin: tyrosine ligase during development and ageing of Caenorhabditis elegans. Gabius, H.J., Graupner, G., Cramer, F. Eur. J. Biochem. (1983) [Pubmed]
  17. Effect of benzimidazole drugs on tubulin in benzimidazole resistant and susceptible strains of Caenorhabditis elegans. Enos, A., Coles, G.C. Int. J. Parasitol. (1990) [Pubmed]
  18. The presenilin protein family member SPE-4 localizes to an ER/Golgi derived organelle and is required for proper cytoplasmic partitioning during Caenorhabditis elegans spermatogenesis. Arduengo, P.M., Appleberry, O.K., Chuang, P., L'Hernault, S.W. J. Cell. Sci. (1998) [Pubmed]
  19. Mutations in a beta-tubulin disrupt spindle orientation and microtubule dynamics in the early Caenorhabditis elegans embryo. Wright, A.J., Hunter, C.P. Mol. Biol. Cell (2003) [Pubmed]
  20. Second harmonic generation imaging of endogenous structural proteins. Mohler, W., Millard, A.C., Campagnola, P.J. Methods (2003) [Pubmed]
  21. Computational prediction of the three-dimensional structures for the Caenorhabditis elegans tubulin family. Gogonea, C.B., Gogonea, V., Ali, Y.M., Merz, K.M., Siddiqui, S.S. J. Mol. Graph. Model. (1999) [Pubmed]
  22. The isolation and in situ location of adligin: the microtubule cross-linking protein from Caenorhabditis elegans. Aamodt, E., Holmgren, R., Culotti, J. J. Cell Biol. (1989) [Pubmed]
  23. Anti-tubulin monoclonal antibodies that bind to specific neurons in Caenorhabditis elegans. Siddiqui, S.S., Aamodt, E., Rastinejad, F., Culotti, J. J. Neurosci. (1989) [Pubmed]
  24. Formation of the first cleavage spindle in nematode embryos. Albertson, D.G. Dev. Biol. (1984) [Pubmed]
  25. Beta-tubulin and benzimidazole resistance in the sheep nematode Haemonchus contortus. Lubega, G.W., Prichard, R.K. Mol. Biochem. Parasitol. (1991) [Pubmed]
 
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