The diverse regulatory roles of FXYD family proteins in modulating NKA activity across different tissues (IMAGE)
Caption
FXYD1, highly expressed in the heart, regulates both Na+ and K+ affinity of NKA. Its phosphorylation at Ser63 or Ser68 enhances NKA activity, whereas the unphosphorylated form inhibits NKA. FXYD2, primarily localized in the thick ascending limb of Henle's loop (TAL), increases Na+ affinity and lowers K+ affinity, contributing to sodium reabsorption; it is regulated by aldosterone and local sodium concentrations. FXYD3 modulates the expression of NKA β1 subunits and reverses glutathionylation, impacting redox-sensitive regulation of pump activity. FXYD4 exhibits high Na+ affinity and plays a role in renal sodium handling, particularly under low sodium or high aldosterone conditions. FXYD5 is associated with increased Na+ affinity and reduced K+ affinity. FXYD6 is co-expressed with the taste receptor channel TRPM5 and contributes to taste signal transduction for sweet, bitter, and umami stimuli. FXYD7, predominantly expressed in neurons, reduces NKA's affinity for K+ but does not affect Na+ binding.
Credit
Xi Li, Min Long, Shangwei Zhong, Junli Luo
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