Function and phylogeny support the independent evolution of an ASIC-like Deg/ENaC channel in the Placozoa.

Function and phylogeny support the independent evolution of an ASIC-like Deg/ENaC channel in the Placozoa.
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DOI:
10.1038/s42003-023-05312-0
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发表时间:
2023-09-18
影响因子:
5.9
通讯作者:
Senatore, Adriano
Senatore, Adriano
中科院分区:
生物学2区
文献类型:
--
作者:
Elkhatib, Wassim;Yanez-Guerra, Luis A.;Mayorova, Tatiana D.;Currie, Mark A.;Singh, Anhadvir;Perera, Maria;Gauberg, Julia;Senatore, Adriano

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ASIC通道是双侧质子门控钠通道,属于大型且功能多样的Deg/ENaC家族,该家族还包括肽门控和机械门控通道。在这里,我们报告说,非双侧无脊椎动物粘毛藻拥有一个质子激活的Deg/ENaC通道,TadNaC 2,具有独特的生物物理特征,包括快速耐受如ASIC 1a,质子敏感性降低如ASIC 2a,双相宏观电流如ASIC 3,以及低敏感性的Deg/ENaC通道阻断剂阿米洛利和Ca 2+离子的组合。结构建模和突变分析表明,TadNaC 2质子门控不同于ASIC通道,缺乏关键的分子决定因素,并涉及手掌和手指区域内的独特残基。系统发育分析表明,T.包括TadNaC 2的adhaerens Deg/ENaC通道在遗传学上不同于ASIC通道,而是与BASIC通道形成进化枝。总之,这项工作表明,ASIC样通道在T。adhaerens和它的门Placozoa。我们的系统发育分析还确定了几个分支的未表征的后生动物Deg/ENaC通道,并提供系统发育证据的存在Deg/ENaC通道外的后生动物,目前在选择单细胞异鞭毛体和丝状体相关物种的基因数据。非双侧的粘毛藻具有质子激活的Deg/ENaC通道,该通道具有ASIC样生物物理特性,但具有不同的质子门控决定因素。还提供了动物外部Deg/ENaC通道存在的系统发育证据。
ASIC channels are bilaterian proton-gated sodium channels belonging to the large and functionally-diverse Deg/ENaC family that also includes peptide- and mechanically-gated channels. Here, we report that the non-bilaterian invertebrate Trichoplax adhaerens possesses a proton-activated Deg/ENaC channel, TadNaC2, with a unique combination of biophysical features including tachyphylaxis like ASIC1a, reduced proton sensitivity like ASIC2a, biphasic macroscopic currents like ASIC3, as well as low sensitivity to the Deg/ENaC channel blocker amiloride and Ca2+ ions. Structural modeling and mutation analyses reveal that TadNaC2 proton gating is different from ASIC channels, lacking key molecular determinants, and involving unique residues within the palm and finger regions. Phylogenetic analysis reveals that a monophyletic clade of T. adhaerens Deg/ENaC channels, which includes TadNaC2, is phylogenetically distinct from ASIC channels, instead forming a clade with BASIC channels. Altogether, this work suggests that ASIC-like channels evolved independently in T. adhaerens and its phylum Placozoa. Our phylogenetic analysis also identifies several clades of uncharacterized metazoan Deg/ENaC channels, and provides phylogenetic evidence for the existence of Deg/ENaC channels outside of Metazoa, present in the gene data of select unicellular heterokont and filasterea-related species. The non-bilaterian Trichoplax adhaerens has a proton-activated Deg/ENaC channel with ASIC-like biophysical properties but distinct determinants for proton gating. Phylogenetic evidence for the existence of Deg/ENaC channels outside of animals is also provided.
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