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.
摘要：
电压门控（Kv）缓慢失活的延迟整流通道调节斑马鱼中空器官的发育。功能通道由电活性Kcnb1（Kv2.1）亚基和Kcng4b（Kv6.4）调节性或无电亚基的四聚体组成。斑马鱼kcng4b基因中的两个突变-kcng4b-C1和kcng4b-C2(Gasanov等人。,2021)-在耳朵发育过程中使用电生理学进行了研究，发育生物学和计算机结构建模。kcng4b-C1突变会导致C端截短，其特征是轻度的Kcng4b功能丧失（LOF），表现为精毛未能扩展和形成异位耳石。相比之下,kcng4b-C2-/-突变导致C端结构域延长，异位第七跨膜（TM）结构域形成，将胞内C端转化为胞外C端。Kcng4b-C2充当Kcng4b功能获得(GOF)等位基因。耳石无法发育，并且kcng4b-C2-/-中的纤毛减少。这些结果表明沉默亚基Kcng4的不同突变可以影响Kv通道的活性并引起广泛的发育缺陷。
