Acetylcholinesterases of Gastrointestinal Nematodes

  • Murray E. Selkirk
  • Ayman S. Hussein


Vertebrate cholinesterases (ChEs) are broadly classified into two families based on their substrate specificity. Acetylcholinesterases (AChEs) terminate transmission of neuronal impulses by rapid hydrolysis of acetylcholine (ACh), and are therefore primarily associated with synaptic contacts in nerves and muscle (Fig. 1).


Pichia Pastoris Parasitic Nematode Cholinesterase Activity Nematode Caenorhabditis Elegans Substrate Buffer 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arpagaus, M., Fedon, Y., Cousin, X., Chatonnet, A., Bergé, J.-B., Fournier, D., and Toutant, J.-P. (1994) cDNA sequence, gene structure, and in vitro expression of ace-1,the gene encoding acetylcholinesterase of class A in the nematode Caenorhabditis elegans J. Biol. Chem. 269,9957–9965.Google Scholar
  2. Arpagaus, M., Richier, P., Bergé, J.-B., and Toutant, J.-P. (1992) Acetylcholinesterases of the nematode Steinernema carpocapsae Characterization of two types of amphiphilic forms differering in their mode of membrane association. Eur. J. Biochem. 207, 11011108.Google Scholar
  3. Austin, L., and Berry, W.K. (1953) Two selective inhibitors of cholinesterase. Biochem. J. 54, 695–700.Google Scholar
  4. Bazelyansky, M., Robey, E., and Kirsch, J. F. (1986) Fractional diffusion-limited component of reactions catalyzed by acetylcholinesterase. Biochemistry 25, 125–30.Google Scholar
  5. Bourne, Y., Taylor, P., and Marchot, P. (1995) Acetylcholinesterase inhibition by fasciculin:crystal structure of the complex. Cell 83, 503–12.Google Scholar
  6. Culetto, E., Combes, D., Fedon, Y., Roig, A., Toutant, J.-P., and Arpagaus, M. (1999) Structure and promoter activity of the 5’ flanking region of ace-1, the gene encoding acetylcholinesterase of class A in Caenorhabditis elegans J. Mol. Biol. 290, 951–66.Google Scholar
  7. Cygler, M., Schrag, J.D., Sussman, J.L., Harel, M., Silman, I., Gentry, M.K., and Doctor, B.P. (1993) Relationship between sequence conservation and three-dimensional structure in a large family of esterases, lipases, and related proteins. Prot. Sci. 2, 366–382.Google Scholar
  8. Dudai, Y., and Silman, I. (1974) Acetylcholinesterase. Meth. Enzymol. 34, 571–580.Google Scholar
  9. Ellman, G.L., Courtney, K.D., Andres, V., and Featherstone, R.M. (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7, 88–95.Google Scholar
  10. Giacobini, E. (1998) Cholinesterase inhibitors for Alzheimer’s disease therapy: from tacrine to future applications. Neurochem. Int. 32, 413–9.Google Scholar
  11. Giles, K. (1997) Interactions underlying subunit associations in cholinesterases. Prot. Eng. 10, 677–685.Google Scholar
  12. Gnagey, A.L., Forte, M., and Rosenberry, T.L. (1987) Isolation and characterization of acetylcholinesterase from Drosophila J. Biol. Chem. 262, 13290–13298.Google Scholar
  13. Grauso, M., Culetto, E., Combes, D., Fedon, Y., Toutant, J.-P., and Arpagaus, M. (1998) Existence of four acetylcholinesterase genes in the nematodes Caenorhabditis elegans and Caenorhabditis briggsae FEBS Lett. 424, 279–284.Google Scholar
  14. Greenfield, S.A. (1991) A non-cholineric action of acetylcholinesterase (AChE) in the brain: from neuronal secretion to the generation of movement. Cell. Mol. Neurobiol. 11, 5577.Google Scholar
  15. Griffiths, G., and Pritchard, D.I. (1994) Purification and biochemical characterisation of acetylcholinesterase (AChE) from the excretory/secretory products of Trichostrongylus colubriformis Parasitology 108,579–586.Google Scholar
  16. Grigg, M.E., Tang, L., Hussein, A.S., and Selkirk, M.E. (1997) Purification and properties of monomeric (G1) forms of acetylcholinesterase secreted by Nippostrongylus brasiliensis Mol. Biochem. Parasitol. 90, 513–524.Google Scholar
  17. Harel, M., Sussman, J.L., Krejci, E., Bon, S., Chanal, P., Massoulié, J., and Silman, I. (1992) Conversion of acetylcholinesterase to butyrylcholinesterase: modelling and mutagenesis. Proc. Natl. Acad. Sci. USA 89, 10827–10831.Google Scholar
  18. Helenius, A., and Simons, K. (1977) Charge shift electrophoresis: simple method for distinguishing between amphiphilic and hydrophilic proteins in detergent solution. Proc. Natl. Acad. Sci. USA 74, 529–532.Google Scholar
  19. Hussein, A.S., Chacôn, M.R., Smith, A.M., Tosado-Acevedo, R., and Selkirk, M.E. (1999) Cloning, expression and properties of a non-neuronal secreted acetylcholinesterase from the parasitic nematode Nippostrongylus brasiliensis J. Biol. Chem. 274, 93129319.Google Scholar
  20. Hussein, A.S., Grigg, M.E., and Selkirk, M.E. (1999) Nippostrongylus brasiliensis Characterisation of a somatic amphiphilic acetylcholinesterase with properties distinct from the secreted enzymes. Exp. Parasitol. 91,144–150.Google Scholar
  21. Hussein, A.S., Smith, A.M., Chacôn, M.R., and Selkirk, M.E. (2000) A second non-neuronal secreted acetylcholinesterase from the parasitic nematode Nippostrongylus brasiliensis determinants of substrate specificity. (Submitted for publication)Google Scholar
  22. Johnson, C.D., Rand, J.R., Herman, R.K., Stern, B.D., and Russell, R.L. (1988) The acetylcholinesterase genes of C. elegans identification of a third gene (ace-3) and mosaic mapping of a synthetic lethal phenotype. Neuron 1, 165–173.Google Scholar
  23. Johnson, C.D., and Russell, R.L. (1975) A rapid, simple radiometric assay for cholinesterase, suitable for multiple determinations. Anal. Biochem. 64, 229–38.Google Scholar
  24. Johnson, C.D., and Russell, R.L. (1983) Multiple molecular forms of acetylcholinesterase in the nematode Caenorhabditis elegans J. Neurochem. 41, 30–46.Google Scholar
  25. Karnovsky, M. J., and Roots, L. (1964) A ‘direct-coloring’ method for cholinesterases. J. Histochem. Cytochem. 12, 219–221.Google Scholar
  26. Kolson, D.L., and Russell, R.L. (1985) A novel class of acetylcholinesterase, revealed by mutations, in the nematode Caenorhabditis elegans J. Neurogenet. 2, 93–110.Google Scholar
  27. Lee, D.L. (1970) The fine structure of the excretory system in adult Nippostrongylus brasiliensis (Nematoda) and a suggested function for the “excretory glands”. Tissue Cell 2, 225–231.Google Scholar
  28. Lee, D.L. (1996) Why do some nematode parasites of the alimentary tract secrete acetylcholinesterase? Int. J. Parasitol. 26, 499–508.Google Scholar
  29. Martin, R.J. (1997) Modes of action of anthelmintic drugs. Vet. J. 154, 11–34.Google Scholar
  30. Massoulié, J., Sussman, J.L., Bon, S., and Silman, I. (1993) Structure and functions of acetylcholinesterase and butyrylcholinesterase. Prog. Brain Res. 98, 139–146.Google Scholar
  31. McLaren, D., Burt, J.S., and Ogilvie, B.M. (1974) The anterior glands of adult Necator americanus (nematoda: strongyloidea)-II. Cytochemical and functional studies. Int. J. Parasitol. 4, 39–46.Google Scholar
  32. Ogilvie, B.M., Rothwell, T.L.W., Bremner, K.C., Schitzerling, H.J., Nolan, J., and Keith, R. K. (1973) Acetylcholinesterase secretion by parasitic nematodes, 1. Evidence for secretion of the enzyme by a number of species. Int. J. Parasitol. 3, 589–597.Google Scholar
  33. Ordentlich, A., Barak, D., Kronman, C., Flashner, Y., Leitner, M., Segall, Y., Ariel, N., Cohen, S., Velan, B., and Shafferman, A. (1993) Dissection of the human acetylcholinesterase active center determinants of substrate specificity. J. Biol. Chem. 268, 17083–17095.Google Scholar
  34. Pritchard, D.I., Leggett, K.V., Rogan, M.T., McKean, P.G., and Brown, A. (1991) Necator americanus secretory acetylcholinesterase and its purification from excretory-secretory products by affinity chromatography. Parasite Immunol. 113,187–199.Google Scholar
  35. Radic, Z., Pickering, N.A., Vellom, D.C., Camp, S., and Taylor, P. (1993) Three distinct domains in the cholinesterase molecule confer selectivity for acetyl-and butyrylcholinesterase inhibitors. Biochemistry 32, 12074–12084.Google Scholar
  36. Rand, J.B., and Nonet, M.L. (1997) Synaptic transmission. C. elegans II. Cold Spring Harbor, New York: Cold Spring Harbor Press, 611–643.Google Scholar
  37. Rhoads, M.L. (1984) Secretory cholinesterases of nematodes: possible functions in the host-parasite relationship. Trop. Vet. 2, 3–10.Google Scholar
  38. Ripoll, D.R., Faerman, C.H., Axelson, P.H., Silman, I., and Sussman, J.L. (1993) An electrostatic mechanism for substrate guidance down the aromatic gorge of acetylcholinesterase. Proc. Natl. Acad. Sci. USA 90, 5128–5132.Google Scholar
  39. Sanders, M., Mathews, B., Sutherland, D., Soong, W., Giles, H., and Pezzementi, L. (1996) Biochemical and molecular characterization of acetylcholinesterase from the hagfish Myxine glutinosa Comp. Biochem. Physiol. 115B, 97–109.Google Scholar
  40. Selkirk, M.E., Hussein, A.S., Russell, W.S., Grigg, M.E., Chacôn, M.R., Smith, A.M., Henson, S., and Tippins, J.R. (1998) Secretory acetylcholinesterases ofGoogle Scholar
  41. Nippostrongylus brasiliensis properties and implications for mucosal immunity. Structure and Function of Cholinesterases and Related Proteins. New York: Plenum Press, 515–522.Google Scholar
  42. Silver, A. (1974) The Biology of Cholinesterases. Amsterdam: North-Holland Publishing Company.Google Scholar
  43. Soreq, H., Patinkin, D., Lev-Lehman, E., Grifman, M., Ginzberg, D., Eckstein, F., and Zakut, H. (1994) Antisense oligonucleotide inhibition of acetylcholinesterase gene expression induces progenitor cell expansion and suppresses hematopoietic apoptosis ex vivo. Proc. Natl. Acad. Sci. USA 91, 7907–11.Google Scholar
  44. Sussman, J.L., Harel, M., Frolow, F., Oefner, C., Goldman, C., Toker, L., and Silman, I. (1991) Atomic structure of acetylcholinesterase from Torpedo californica a prototypic acetylcholine-binding protein. Science 253, 872–879.Google Scholar
  45. Taylor, P. (1991) The cholinesterases. J. Biol. Chem. 266, 4025–4028.Google Scholar
  46. Taylor, P., and Radic, Z. (1994) The cholinesterases: from genes to proteins. Annu. Rev. Pharmacol. Toxicol. 34, 281–320.Google Scholar
  47. Toutant, J.-P. (1986) An evaluation of the hydrophobic interactions of chick muscle acetylcholinesterase by charge shift electrophoresis and gradient centrifugation. Neurochem. Int. 9, 111–119.Google Scholar
  48. Toutant, J.-P. (1989) Insect acetylcholinesterase: catalytic properties, tissue distribution and molecular forms. Prog. Neurobiol. 32, 423–446.Google Scholar
  49. Vellom, D.C., Radic, Z., Li, Y., Pickering, N.A., Camp, S., and Taylor, P. (1993) Amino acid residues controlling acetylcholinesterase and butyrylcholinesterase specificity. Biochemistry 32, 12–17.Google Scholar
  50. Wilson, LB., Bergmann, F., and Nachmansohn, D. (1950) Acetylcholinesterase X. Mechanism of the catalysis of acylation reactions. J. Biol. Chem. 186, 781–790.Google Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Murray E. Selkirk
    • 1
  • Ayman S. Hussein
    • 1
  1. 1.Department of BiochemistryImperial College of Science, Technology and MedicineLondonUK

Personalised recommendations