Early vertebrate origin and diversification of small transmembrane regulators of cellular ion transport

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12399-list-0001">Small transmembrane proteins such as FXYDs, which interact with Na⁺,K⁺‐ATPase, and the micropeptides that interact with sarco/endoplasmic reticulum Ca²⁺‐ATPase play fundamental roles in regulation of ion transport in vertebrates.Uncertain evolutionary origins and phylogenetic relationships among these regulators of ion transport have led to inconsistencies in their classification across vertebrate species, thus hampering comparative studies of their functions.We discovered the first FXYD homologue in sea lamprey, a basal jawless vertebrate, which suggests small transmembrane regulators of ion transport emerged early in the vertebrate lineage.We also identified 13 gene subfamilies of FXYDs and propose a revised, phylogeny‐based FXYD classification that is consistent across vertebrate species.These findings provide an improved framework for investigating physiological and pathophysiological functions of small transmembrane regulators of ion transport.