PUBLICATION
Mutant analysis of Kcng4b reveals how the different functional states of the voltage-gated potassium channel regulate ear development
- Authors
- Jędrychowska, J., Vardanyan, V., Wieczor, M., Marciniak, A., Czub, J., Amini, R., Jain, R., Shen, H., Choi, H., Kuznicki, J., Korzh, V.
- ID
- ZDB-PUB-240317-11
- Date
- 2024
- Source
- Developmental Biology 513: 50-62 (Journal)
- Registered Authors
- Jain, Ruchi, Jędrychowska, Justyna, Korzh, Vladimir, Kuznicki, Jacek, Shen, Hongyuan
- Keywords
- CRISPR-Cas9 site-specific mutagenesis, Gain-of-function, Kinocilia, Loss-of-function, Otolith, Silent α-subunit, Zebrafish
- MeSH Terms
-
- Animals
- Ear*/embryology
- Mutation/genetics
- Voltage-Dependent Anion Channels*/genetics
- Voltage-Dependent Anion Channels*/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 38492873 Full text @ Dev. Biol.
Citation
Jędrychowska, J., Vardanyan, V., Wieczor, M., Marciniak, A., Czub, J., Amini, R., Jain, R., Shen, H., Choi, H., Kuznicki, J., Korzh, V. (2024) Mutant analysis of Kcng4b reveals how the different functional states of the voltage-gated potassium channel regulate ear development. Developmental Biology. 513:50-62.
Abstract
The voltage gated (Kv) slow-inactivating delayed rectifier channel regulates the development of hollow organs of the zebrafish. The functional channel consists of the tetramer of electrically active Kcnb1 (Kv2.1) subunits and Kcng4b (Kv6.4) modulatory or electrically silent subunits. The two mutations in zebrafish kcng4b gene - kcng4b-C1 and kcng4b-C2 (Gasanov et al., 2021) - have been studied during ear development using electrophysiology, developmental biology and in silico structural modelling. kcng4b-C1 mutation causes a C-terminal truncation characterized by mild Kcng4b loss-of-function (LOF) manifested by failure of kinocilia to extend and formation of ectopic otoliths. In contrast, the kcng4b-C2-/- mutation causes the C-terminal domain to elongate and the ectopic seventh transmembrane (TM) domain to form, converting the intracellular C-terminus to an extracellular one. Kcng4b-C2 acts as a Kcng4b gain-of-function (GOF) allele. Otoliths fail to develop and kinocilia are reduced in kcng4b-C2-/-. These results show that different mutations of the silent subunit Kcng4 can affect the activity of the Kv channel and cause a wide range of developmental defects.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping