Skip to main content
Log in

Most Acetylcholinesterase Activity of Non-Nervous Tissues and Cells Arises from the AChE-H Transcript

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

While the functional implications of AChE-T, PRiMA and ColQ have been firmly established, those of glypiated AChE remain uncertain. Insights into the physiological meaning of glycosylphosphatidylinositol (GPI)-linked AChE-H were gained by comparing nervous and non-nervous tissues for the amount of AChE mRNA variants they contained. PCR showed that AChE-T mRNA prevailed in the mouse brain, spinal cord, sciatic nerve and muscle, and AChE-H mRNA in the bone marrow and thymus, as well as in the human gut. The similar levels of AChE-T and AChE-H mRNAs in mouse liver and human kidney contrasted with the almost exclusive presence of catalytically active AChE-H in both organs. The absence of PRiMA mRNA in liver suggested that the tetramers made of AChE-T fail to bind to the cell membrane and are secreted due to the lack of PRiMA in non-nervous organs. In contrast, glypiated AChE-H is largely and lastingly bound to the cell membrane. Thus, non-synaptic glypiated AChE-H seems to be the counterpart of synaptic PRiMA-linked AChE-T, the former designed for clearing ACh waves, the latter for confronting ACh bursts, and both for helping to protect cells against the harmful effects of durable nicotinic and muscarinic activation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

AChE:

Acetylcholinesterase

BuChE:

Butyrylcholinesterase

GPI:

Glycosylphosphatidylinositol

mAChR:

Muscarinic acetylcholine receptor

nAChR:

Nicotinic acetylcholine receptor

PIPLC:

Phosphatidylinositol-specific phospholipase C

PRiMA:

Proline-rich membrane anchor

References

  • Abreu-Villaca Y, Filgueiras CC, Manhaes AC (2011) Developmental aspects of the cholinergic system. Behav Brain Res 221:367–378

    Article  CAS  PubMed  Google Scholar 

  • Arpagaus M, Kott M, Vatsis KP, Bartels CF, La Du BN, Lockridge O (1990) Structure of the gene for human butyrylcholinesterase. Evidence for a single copy. Biochemistry 29:124–131

    Article  CAS  PubMed  Google Scholar 

  • Bernard V, Girard E, Hrabovska A, Camp S, Taylor P, Plaud B, Krejci E (2011) Distinct localization of collagen Q and PRiMA forms of acetylcholinesterase at the neuromuscular junction. Mol Cell Neurosci 46:272–281

    Article  CAS  PubMed  Google Scholar 

  • Biberoglu K, Schopfer LM, Tacal O, Lockridge O (2012) The proline-rich tetramerization peptides in equine serum butyrylcholinesterase. FEBS J 279:3844–3858

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cabezas-Herrera J, Moral-Naranjo MT, Campoy FJ, Vidal CJ (1994) G4 forms of acetylcholinesterase and butyrylcholinesterase in normal and dystrophic mouse muscle differ in their interaction with Ricinus communis agglutinin. Biochim Biophys Acta 1225:283–288

    Article  CAS  PubMed  Google Scholar 

  • Cabezas-Herrera J, Moral-Naranjo MT, Campoy FJ, Vidal CJ (1997) Glycosylation of acetylcholinesterase forms in microsomal membranes from normal and dystrophic Lama2dy mouse muscle. J Neurochem 69:1964–1974

    Article  CAS  PubMed  Google Scholar 

  • Chen VP, Choi RC, Chan WK, Leung KW, Guo AJ, Chan GK, Luk WK, Tsim KW (2011) The assembly of proline-rich membrane anchor (PRiMA)-linked acetylcholinesterase enzyme: glycosylation is required for enzymatic activity but not for oligomerization. J Biol Chem 286:32948–32961

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dvir H, Silman I, Harel M, Rosenberry TL, Sussman JL (2010) Acetylcholinesterase: from 3D structure to function. Chem Biol Interact 187:10–22

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gahring LC, Rogers SW (2005) Neuronal nicotinic acetylcholine receptor expression and function on nonneuronal cells. AAPS J 7:E885–E894

    Article  CAS  PubMed Central  Google Scholar 

  • García-Ayllón MS, Silveyra MX, Candela A, Compañ A, Clària J, Jover R, Pérez-Mateo M, Felipo V, Martínez S, Galcerán J, Sáez-Valero J (2006) Changes in liver and plasma acetylcholinesterase in rats with cirrhosis induced by bile duct ligation. Hepatology 43:444–453

    Article  PubMed  Google Scholar 

  • Gómez JL, García-Ayllón MS, Campoy FJ, Vidal CJ (2000) Muscular dystrophy alters the processing of light acetylcholinesterase but not butyrylcholinesterase forms in liver of Lama2dy mice. J Neurosci Res 62:134–145

    Article  PubMed  Google Scholar 

  • Gómez JL, Moral-Naranjo MT, Campoy FJ, Vidal CJ (1999) Characterization of acetylcholinesterase and butyrylcholinesterase forms in normal and dystrophic Lama2dy mouse heart. J Neurosci Res 56:295–306

    Article  PubMed  Google Scholar 

  • Heider H, Brodbeck U (1992) Monomerization of tetrameric bovine caudate nucleus acetylcholinesterase. Implications for hydrophobic assembly and membrane anchor attachment site. Biochem J 281:279–284

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ishii M, Kurachi Y (2006) Muscarinic acetylcholine receptors. Curr Pharm Des 12:3573–3581

    Article  CAS  PubMed  Google Scholar 

  • Karczmar AG (2010) Cholinesterases (ChEs) and the cholinergic system in ontogenesis and phylogenesis, and non-classical roles of cholinesterases—a review. Chem Biol Interact 187:34–43

    Article  CAS  PubMed  Google Scholar 

  • Karmouch J, Dobbertin A, Sigoillot S, Legay C (2013) Developmental consequences of the ColQ/MuSK interactions. Chem Biol Interact 203:287–291

    Article  CAS  PubMed  Google Scholar 

  • Kawashima K, Fujii T, Moriwaki Y, Misawa H, Horiguchi K (2012) Reconciling neuronally and nonneuronally derived acetylcholine in the regulation of immune function. Ann N Y Acad Sci 1261:7–17

    Article  CAS  PubMed  Google Scholar 

  • Kimbell LM, Ohno K, Engel AG, Rotundo RL (2004) C-terminal and heparin-binding domains of collagenic tail subunit are both essential for anchoring acetylcholinesterase at the synapse. J Biol Chem 279:10997–11005

    Article  CAS  PubMed  Google Scholar 

  • Kummer W, Lips KS, Pfeil U (2008) The epithelial cholinergic system of the airways. Histochem Cell Biol 130:219–234

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Martínez-Moreno P, Nieto-Cerón S, Torres-Lanzas J, Ruiz-Espejo F, Tovar-Zapata I, Martínez-Hernández P, Rodríguez-López JN, Vidal CJ, Cabezas-Herrera J (2006) Cholinesterase activity of human lung tumours varies according to their histological classification. Carcinogenesis 27:429–436

    Article  PubMed  Google Scholar 

  • Massoulié J, Bon S, Perrier N, Falasca C (2005) The C-terminal peptides of acetylcholinesterase: cellular trafficking, oligomerization and functional anchoring. Chem Biol Interact 157–158:3–14

    Article  PubMed  Google Scholar 

  • Massoulié J, Perrier N, Noureddine H, Liang D, Bon S (2008) Old and new questions about cholinesterases. Chem Biol Interact 175:30–44

    Article  PubMed  Google Scholar 

  • Meshorer E, Soreq H (2006) Virtues and woes of AChE alternative splicing in stress-related neuropathologies. Trends Neurosci 29:216–224

    Article  CAS  PubMed  Google Scholar 

  • Montenegro MF, Ruiz-Espejo F, Campoy FJ, Muñoz-Delgado E, Páez de la Cadena M, Rodríguez-Berrocal FJ, Vidal CJ (2006) Cholinesterases are down-expressed in human colorectal carcinoma. Cell Mol Life Sci 63:2175–2182

    Article  CAS  PubMed  Google Scholar 

  • Moral-Naranjo MT, Cabezas-Herrera J, Vidal CJ, Campoy FJ (2002) Muscular dystrophy with laminin deficiency decreases the content of butyrylcholinesterase tetramers in sciatic nerves of Lama2dy mice. Neurosci Lett 331:155–158

    Article  CAS  PubMed  Google Scholar 

  • Moral-Naranjo MT, Montenegro MF, Muñoz-Delgado E, Campoy FJ, Vidal CJ (2010) The levels of both lipid rafts and raft-located acetylcholinesterase dimers increase in muscle of mice with muscular dystrophy by merosin deficiency. Biochim Biophys Acta 1802:754–764

    Article  CAS  PubMed  Google Scholar 

  • Muñoz-Delgado E, Montenegro MF, Campoy FJ, Moral-Naranjo MT, Cabezas-Herrera J, Kovacs G, Vidal CJ (2010) Expression of cholinesterases in human kidney and its variation in renal cell carcinoma types. FEBS J 277:4519–4529

    Article  PubMed  Google Scholar 

  • Nieto-Cerón S, Moral-Naranjo MT, Muñoz-Delgado E, Vidal CJ, Campoy FJ (2004) Molecular properties of acetylcholinesterase in mouse spleen. Neurochem Int 45:129–139

    Article  PubMed  Google Scholar 

  • Nieto-Cerón S, Sánchez del Campo LF, Muñoz-Delgado E, Vidal CJ, Campoy FJ (2005) Muscular dystrophy by merosin deficiency decreases acetylcholinesterase activity in thymus of Lama2dy mice. J Neurochem 95:1035–1046

    Article  PubMed  Google Scholar 

  • Pezzementi L, Nachon F, Chatonnet A (2011) Evolution of acetylcholinesterase and butyrylcholinesterase in the vertebrates: an atypical butyrylcholinesterase from the Medaka Oryzias latipes. PLoS One 6:e17396

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rosas-Ballina M, Tracey KJ (2009) Cholinergic control of inflammation. J Inter Med 265:663–679

    Article  CAS  Google Scholar 

  • Sáez-Valero J, Tornel PL, Muñoz-Delgado E, Vidal CJ (1993) Amphiphilic and hydrophilic forms of acetyl- and butyrylcholinesterase in human brain. J Neurosci Res 35:678–689

    Article  PubMed  Google Scholar 

  • Sáez-Valero J, Vidal CJ (1995) Monomers and dimers of acetylcholinesterase in human meningioma are anchored to the membrane by glycosylphosphatidylinositol. Neurosci Lett 195:101–104

    Article  PubMed  Google Scholar 

  • Sánchez del Campo LF, Nieto-Cerón S, Morote-García JC, Muñoz-Delgado E, Vidal CJ, Campoy FJ (2007) Butyrylcholinesterase activity and molecular components in thymus of healthy and merosin-deficient Lama2dy mice. Neurochem Int 50:531–539

    Article  PubMed  Google Scholar 

  • Taylor P (1991) The cholinesterases. J Biol Chem 266:4025–4028

    CAS  PubMed  Google Scholar 

  • Warren GW, Singh AK (2013) Nicotine and lung cancer. J Carcinog 12:1

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wessler I, Kirkpatrick CJ (2008) Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans. Brit J Pharmacol 154:1558–1571

    Article  CAS  Google Scholar 

  • Xie HQ, Choi RC, Leung KW, Siow NL, Kong LW, Lau FT, Peng HB, Tsim KW (2007) Regulation of a transcript encoding the proline-rich membrane anchor of globular muscle acetylcholinesterase. The suppressive roles of myogenesis and innervating nerves. J Biol Chem 282:11765–11775

    Article  CAS  PubMed  Google Scholar 

  • Xie W, Stribley JA, Chatonnet A, Wilder PJ, Rizzino A, McComb RD, Taylor P, Hinrichs SH, Lockridge O (2000) Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase. J Pharmacol Exp Ther 293:896–902

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cecilio J. Vidal.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Montenegro, M.F., Nieto-Cerón, S., Cabezas-Herrera, J. et al. Most Acetylcholinesterase Activity of Non-Nervous Tissues and Cells Arises from the AChE-H Transcript. J Mol Neurosci 53, 429–435 (2014). https://doi.org/10.1007/s12031-013-0172-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-013-0172-8

Keywords

Navigation