Mutation of a serine near the catalytic site of the choline acetyltransferase a gene almost completely abolishes motility of the zebrafish embryo

• Published in: PloS one Vol. 13; no. 11; p. e0207747
• Main Authors: Joshi, Swarnima, Virdi, Sanamjeet, Etard, Christelle, Geisler, Robert, Strähle, Uwe
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20-11-2018; Public Library of Science (PLoS)
• Subjects: Acetylcholine; Acetyltransferase; Arginine; Bioinformatics; Biology and Life Sciences; Catalysis; Choline; Choline O-acetyltransferase; Congenital defects; Congenital diseases; Crystal structure; Danio rerio; Embryos; Enzymatic activity; Ethyl nitrosourea; Genetics; Genomes; Internet; Missense mutation; Motility; Mutagenesis; Mutants; Mutation; Myasthenia; Nervous system; Neuromuscular junctions; Neuromuscular transmission; Physical Sciences; Poultry; Protein structure; Proteins; Research and Analysis Methods; Serine; Synthesis; Toxicology; Zebrafish; United States > US; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0207747

In zebrafish, the gene choline acetyltransferase a (chata) encodes one of the two ChAT orthologs responsible for the synthesis of acetylcholine. Acetylcholine (ACh) is essential for neuromuscular transmission and its impaired synthesis by ChAT can lead to neuromuscular junction disorders such as congenital myasthenic syndromes in humans. We have identified a novel mutation in the chata gene of zebrafish, chatatk64, in a collection of uncharacterised ENU-induced mutants. This mutant carries a missense mutation in the codon of a highly conserved serine changing it to an arginine (S102R). This serine is conserved among ChATs from zebrafish, rat, mice and chicken to humans. It resides within the catalytic domain and in the vicinity of the active site of the enzyme. However, it has not been reported so far to be required for enzymatic activity. Modelling of the S102R variant change in the ChAT protein crystal structure suggests that the change affects protein structure and has a direct impact on the catalytic domain of the protein which abolishes embryo motility almost completely.