PUBLICATION

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

Authors
Joshi, S., Virdi, S., Etard, C., Geisler, R., Strähle, U.
ID
ZDB-PUB-181127-23
Date
2018
Source
PLoS One   13: e0207747 (Journal)
Registered Authors
Etard, Christelle, Geisler, Robert, Joshi, Swarnima, Strähle, Uwe, Virdi, Sanamjeet
Keywords
none
MeSH Terms
  • Alleles
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Catalytic Domain*
  • Choline O-Acetyltransferase/chemistry*
  • Choline O-Acetyltransferase/genetics*
  • Choline O-Acetyltransferase/metabolism
  • Embryo, Nonmammalian/physiology*
  • Enzyme Stability
  • Humans
  • Movement*
  • Mutation, Missense
  • Protein Structure, Secondary
  • Serine*
  • Zebrafish/embryology*
  • Zebrafish/genetics
PubMed
30458023 Full text @ PLoS One
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes