Activation by cleavage of the epithelial Na+ channel α and γ subunits independently coevolved with the vertebrate terrestrial migration

eLife

Nathan L Clark¹  Clayton Gentilcore²  Xue-Ping Wang²  Deidra M Balchak²  Ossama B Kashlan³ 

[1]Department of Human Genetics, University of Utah, Salt Lake City, United States

[2]Department of Medicine, University of Pittsburgh, Pittsburgh, United States

[3]Department of Medicine, University of Pittsburgh, Pittsburgh, United States

[4]Computational and Systems Biology, University of Pittsburgh, Pittsburgh, United States

关键词: E. calabaricus;    N. forsteri;    epithelial Na+ channel;    proteolytic activation;    furin;    vertebrate land invasion;    Xenopus;    Other;   

DOI  :  10.7554/eLife.75796

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY