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 was required for terrestrial survival.

中文翻译：

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与脊椎动物陆地迁移独立共同进化的上皮 Na+ 通道 α 和 γ 亚基的裂解激活

脊椎动物进化出钠保护和气体交换机制，以及从水生栖息地向陆地栖息地的迁移。上皮细胞 Na ⁺通道 (ENaC) 功能对于负责细胞外液稳态和气体交换的系统至关重要。ENaC 通过在多个特定细胞外多碱基位点的切割激活，从通道的 α 和 γ 亚基释放抑制性束。我们发现 ENaC 亚基中的近端和远端多碱基束共同进化，这与在哺乳动物中观察到的激活的双重裂解要求一致。Polybasic 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。总之，当陆地生存需要肾脏 Na ⁺保守和肺泡气体交换时，ENaC 中蛋白酶激活位点在脊椎动物中发育。