Activation by cleavage of the epithelial Na(+) channel α and γ subunits independently coevolved with the vertebrate terrestrial migration.
Activation by cleavage of the epithelial Na(+) channel α and γ subunits independently coevolved with the vertebrate terrestrial migration.
复制标题
DOI：
10.7554/elife.75796
复制
发表时间：
2022-01-05
期刊：
影响因子：
7.7
通讯作者：
Kashlan OB
中科院分区：
文献类型：
--
作者：
Wang XP;Balchak DM;Gentilcore C;Clark NL;Kashlan OB
脊椎动物在从水生栖息地迁移到陆地栖息地的过程中进化出了钠保存和气体交换机制。上皮Na+通道（ENaC）功能对负责细胞外液体稳态和气体交换的系统至关重要。ENaC通过在多个特定的细胞外多基位点的切割激活，从通道的α和γ亚基释放抑制束。我们发现ENaC亚基的近端多基束和远端多基束共同进化，这与在哺乳动物中观察到的双切割激活要求一致。多基束对随着陆地迁移和肺的出现而进化，与ENaC激活剂醛固酮一致，并独立出现在α和γ亚基中。综上所述，在脊椎动物中，当肾脏Na+保护和肺泡气体交换是陆地生存所必需的时候，ENaC中蛋白酶激活的位点就出现了。
Vertebrates evolved mechanisms for sodium conservation and gas exchange in conjunction with migration from aquatic to terrestrial habitats. Epithelial Na+ channel (ENaC) function is critical to systems responsible for extracellular fluid homeostasis and gas exchange. ENaC is activated by cleavage at multiple specific extracellular polybasic sites, releasing inhibitory tracts from the channel’s α and γ subunits. We found that proximal and distal polybasic tracts in ENaC subunits coevolved, consistent with the dual cleavage requirement for activation observed in mammals. Polybasic tract pairs evolved with the terrestrial migration and the appearance of lungs, coincident with the ENaC activator aldosterone, and appeared independently in the α and γ subunits. In summary, sites within ENaC for protease activation developed in vertebrates when renal Na+ conservation and alveolar gas exchange were required for terrestrial survival.