KIT | KIT-Bibliothek | Impressum | Datenschutz
Open Access Logo
§
Verlagsausgabe
DOI: 10.5445/IR/1000087886
Veröffentlicht am 26.11.2018
Originalveröffentlichung
DOI: 10.1371/journal.pone.0207747

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

Joshi, Swarnima; Virdi, Sanamjeet; Etard, Christelle; Geisler, Robert; Strähle, Uwe

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.


Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Jahr 2018
Sprache Englisch
Identifikator ISSN: 1932-6203
URN: urn:nbn:de:swb:90-878868
KITopen-ID: 1000087886
HGF-Programm 47.01.01 (POF III, LK 01)
Erschienen in PLOS ONE
Band 13
Heft 11
Seiten e0207747
Vorab online veröffentlicht am 20.11.2018
Nachgewiesen in Scopus
KIT – Die Forschungsuniversität in der Helmholtz-Gemeinschaft KITopen Landing Page