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Mutant analysis of Kcng4b reveals how the different functional states of the voltage-gated potassium channel regulate ear development.
Jedrychowska, Justyna; Vardanyan, Vitya; Wieczor, Milosz; Marciniak, Antoni; Czub, Jacek; Amini, Razieh; Jain, Ruchi; Shen, Hongyuan; Choi, Hyungwon; Kuznicki, Jacek; Korzh, Vladimir.
Afiliação
  • Jedrychowska J; International Institute of Molecular and Cell Biology in Warsaw, Poland; Department of Genetics, Institute of Physiology and Pathology of Hearing, Warsaw, Poland.
  • Vardanyan V; Institute of Molecular Biology, Armenian Academy of Sciences, Yerevan, Armenia.
  • Wieczor M; Department of Physical Chemistry, Gdansk University of Technology, Gdansk, Poland.
  • Marciniak A; Department of Physical Chemistry, Gdansk University of Technology, Gdansk, Poland.
  • Czub J; Department of Physical Chemistry, Gdansk University of Technology, Gdansk, Poland.
  • Amini R; International Institute of Molecular and Cell Biology in Warsaw, Poland.
  • Jain R; International Institute of Molecular and Cell Biology in Warsaw, Poland.
  • Shen H; Singapore Nuclear Research and Safety Initiative, National University of Singapore, Singapore.
  • Choi H; Cardiovascular Research Institute, National University Health Sciences, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Kuznicki J; International Institute of Molecular and Cell Biology in Warsaw, Poland.
  • Korzh V; International Institute of Molecular and Cell Biology in Warsaw, Poland. Electronic address: vkorzh@iimcb.gov.pl.
Dev Biol ; 513: 50-62, 2024 Sep.
Article em En | MEDLINE | ID: mdl-38492873
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peixe-Zebra / Proteínas de Peixe-Zebra / Orelha / Canais de Ânion Dependentes de Voltagem Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peixe-Zebra / Proteínas de Peixe-Zebra / Orelha / Canais de Ânion Dependentes de Voltagem Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article