| RRC ID |
70182
|
| 著者 |
Kawai T, Hashimoto M, Eguchi N, Nishino JM, Jinno Y, Mori-Kreiner R, Aspåker M, Chiba D, Ohtsuka Y, Kawanabe A, Nishino AS, Okamura Y.
|
| タイトル |
Heterologous functional expression of ascidian Nav1 channels and close relationship with the evolutionary ancestor of vertebrate Nav channels.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Voltage-gated sodium channels (Nav1s) are responsible for the initiation and propagation of action potentials in neurons, muscle, and endocrine cells. Many clinically used drugs such as local anesthetics and antiarrhythmics inhibit Nav1s, and a variety of inherited human disorders are caused by mutations in Nav1 genes. Nav1s consist of the main α subunit and several auxiliary β subunits. Detailed information on the structure-function relationships of Nav1 subunits has been obtained through heterologous expression experiments and analyses of protein structures. The basic properties of Nav1s, including their gating and ion permeation, were classically described in the squid giant axon and other invertebrates. However, heterologous functional expression of Nav1s from marine invertebrates has been unsuccessful. Ascidians belong to the Urochordata, a sister group of vertebrates, and the larval central nervous system of ascidians shows a similar plan to that of vertebrates. Here, we report the biophysical properties of ascidian Ciona Nav1 (CiNav1a) heterologously expressed in Xenopus oocytes. CiNav1a exhibited tetrodotoxin-insensitive sodium currents with rapid gating kinetics of activation and inactivation. Furthermore, consistent with the fact that the Ciona genome lacks orthologous genes to vertebrate β subunits, the human β1 subunit did not influence the gating properties when coexpressed with CiNav1a. Interestingly, CiNav1a contains an ankyrin-binding motif in the II-III linker, which can be targeted to the axon initial segment of mammalian cortical neurons. Our findings provide a platform to gain insight into the evolutionary and biophysical properties of Nav1s, which are important for the development of targeted therapeutics.
|
| 巻・号 |
296
|
| ページ |
100783
|
| 公開日 |
2021-1-1
|
| DOI |
10.1016/j.jbc.2021.100783
|
| PII |
S0021-9258(21)00576-7
|
| PMID |
34000300
|
| PMC |
PMC8192821
|
| MeSH |
Animals
Ciona intestinalis / genetics
Ciona intestinalis / metabolism*
Gene Expression
Phylogeny
Sodium / metabolism
Voltage-Gated Sodium Channels / genetics
Voltage-Gated Sodium Channels / metabolism*
Xenopus
|
| IF |
4.238
|
| リソース情報 |
| カタユウレイボヤ・(ニッポンウミシダ) |
Wild C. int |
