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

Joshi, Swarnima 1; Virdi, Sanamjeet 1; Etard, Christelle 1; Geisler, Robert 1; Strähle, Uwe 1
1 Institut für Toxikologie und Genetik (ITG), Karlsruher Institut für Technologie (KIT)


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.

Verlagsausgabe §
DOI: 10.5445/IR/1000087886
Veröffentlicht am 26.11.2018
DOI: 10.1371/journal.pone.0207747
Zitationen: 3
Web of Science
Zitationen: 4
Zitationen: 6
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2018
Sprache Englisch
Identifikator ISSN: 1932-6203
KITopen-ID: 1000087886
HGF-Programm 47.01.01 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in PLOS ONE
Verlag Public Library of Science (PLoS)
Band 13
Heft 11
Seiten e0207747
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Vorab online veröffentlicht am 20.11.2018
Nachgewiesen in Scopus
Web of Science
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