Allelic variants of acetylcholinesterase: genetic evidence that all acetylcholinesterase forms in avian nerves and muscles are encoded by a single gene.

Rotundo, Richard L.; Gómez, Alejandro Raúl Gratacós; Fernández‐Valle, Cristina; Randall, William R.

doi:10.1073/pnas.85.20.7805

Cited by 36 publications

(14 citation statements)

References 37 publications

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“…The catalytic subunits of all forms of AcChoEase are encoded by a single gene. In the case of chicken, this was demonstrated by Rotundo et al (2), by an analysis of two allelic forms, a and A, differing by their mass in sodium dodecyl sulfate/ polyacrylamide gel electrophoresis.…”

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confidence: 96%

Existence of an inactive pool of acetylcholinesterase in chicken brain.

Châtel

Grassi

Frobert

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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We analyzed acetyicholinesterase (AcChoEase; EC 3.1.1.7) activity and AcChoEase immunoreactive protein in chicken brain by using five monoclonal antibodies raised against chicken AcChoEase. Four of them specifically recognized AcChoEase catalytic subunits in Western blots and one, C-131, recognized only enzymaticafly active AcChoEase. We observed considerable differences in the ratio of immunoreactive protein to catalytic activity in various fractions, indicating the existence of inactive AcChoEase protein. This inactive AcChoEase component was more abundant in a low-saltsoluble extract than in a subsequent detergent-soluble extract. On the basis of the ratio between activity and immunoreactivity, we calculated that the inactive component represents about 30% of the total AcChoEase subunits in chicken brain. The immunoreactive AcChoEase protein sedimented in sucrose gradients like the active molecular forms; the G1 and G2 peaks contained inactive molecules, whereas the G4 peak appeared to contain only active AcChoEase. The bulk of inactive AcChoEase reacted with the organophosphate cholinesterase inhibitor O-ethyl S-[2-(diisopropylamino)ethylJmethylphosphonothioate (MTP) but was found to bind the active site affinity ligand N-methylacridinium poorly and was not recognized by the active-form-specific monoclonal antibody, C-131. In addition, most of this fraction is sensitive to endoglycosidase H and binds the lectin wheat germ agglutinin poorly, suggesting that it was not processed in the Golgi apparatus. From these observations, we propose that the active and inactive AcChoEase components are differently folded.Acetylcholinesterase (AcChoEase; EC 3.1.1.7) presents a panoply of molecular forms consisting of monomers (Ga), homo-oligomers (dimers, G2, and tetramers, G4), and heterooligomers which incorporate structural as well as catalytic subunits (collagen-tailed or asymmetric forms and hydrophobic-tailed tetramers) (for review, see ref.

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confidence: 96%

Existence of an inactive pool of acetylcholinesterase in chicken brain.

Châtel

Grassi

Frobert

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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“…Several hypotheses may be considered to explain the production of this unusual type of AChE in venom glands. First, although previously studied vertebrates possess a single AChE gene (11)(12)(13)(14), the snake might possess two distinct AChE genes, expressed in cholinergic tissues and the venom glands, respectively. Such a duplication would be similar to the duplication of cholinesterase genes, which generate the twin enzymes AChE and butyrylcholinesterase (BChE) (EC 3.1.1.8) in vertebrates (15).…”

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confidence: 99%

“…: 33-1-45688685; Fax: 33-1-40613057; E-mail: cbon@pasteur.fr. 1 The abbreviations used are: AChE, acetylcholinesterase; A 8 and A 12 , asymmetric forms composed of two or three AChE tetramers, associated with a triple helical collagen tail; AChE H , AChE S , and AChE T , AChE subunits of type H, S and T, generated from transcripts terminating with the H, S, and T exons; AChE gT , construction containing the intron that precedes exon T; AChE ⌬ , truncated AChE subunit limited to the catalytic domain; BChE, butyrylcholinesterase; G 1 a , G 2 a , and G 4 a , amphiphilic globular monomer, dimer, and tetramer, respectively; G 1 na and G 4 na , nonamphiphilic globular monomer and tetramer; GPI, glycophosphatidylinositol; iso-OMPA, tetraisopropyl pyrophos-lated to the fact that the venom AChE possesses a specific C-terminal peptide, which we called SARA after its last four residues: this peptide is highly hydrophilic and does not contain any cysteine residue that could establish intersubunit disulfide bonds. It defines AChE S subunits, which produce only soluble monomers when expressed in COS cells (7).…”

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confidence: 99%

Identification of a Novel Type of Alternatively Spliced Exon from the Acetylcholinesterase Gene of Bungarus fasciatus

Cousin¹,

Bon²,

Massoulié³

et al. 1998

Journal of Biological Chemistry

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The venom of the snake Bungarus fasciatus contains a hydrophilic, monomeric species of acetylcholinesterase (AChE), characterized by a C-terminal region that does not resemble the alternative T-or H-peptides. Here, we show that the snake contains a single gene for AChE, possessing a novel alternative exon (S) that encodes the C-terminal region of the venom enzyme, located downstream of the T exon. Alternative splicing generates S mRNA in the venom gland and S and T mRNAs in muscle and liver. We found no evidence for the presence of an H exon between the last common "catalytic" exon and the T exon, where H exons are located in Torpedo and in mammals. Moreover, COS cells that were transfected with AChE expression vectors containing the T exon with or without the preceding genomic region produced exclusively AChE T subunits. In the snake tissues, we could not detect any glycophosphatidylinositol-anchored AChE form that would have derived from H subunits. In the liver, the cholinesterase activity comprises both AChE and butyrylcholinesterase components; butyrylcholinesterase corresponds essentially to nonamphiphilic tetramers and AChE to nonamphiphilic monomers (G 1 na ). In muscle, AChE is largely predominant: it consists of globular forms (G 1 a and G 4 a ) and trace amounts of asymmetric forms (A 8 and A 12 ), which derive from AChE T subunits. Thus, the Bungarus AChE gene possesses alternatively spliced T and S exons but no H exon; the absence of an H exon may be a common feature of AChE genes in reptiles and birds.

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“…Nothing is known about the gene structure of the tetrameric globular 04 AChE form. In avian nerves and muscles genetic evidence indicated that all AChE forms arise from a single gene (Rotundo et al, 1988). However, recent studies in rat muscle suggests that the G 4 AChE form might have a different origin than the A12 and G2 AChE .…”

Section: The Molecular A~ and Gz Forms Of Ache Arise From A Single Gementioning

confidence: 99%