Regulation of Na+/K+ ATPase transport velocity by RNA editing.
Because firing properties and metabolic rates vary widely, neurons require different transport rates from their Na(+)/K(+) pumps in order to maintain ion homeostasis. In this study we show that Na(+)/K(+) pump activity is tightly regulated by a novel process, RNA editing. Three codons within the squid Na(+)/K(+) ATPase gene can be recoded at the RNA level, and the efficiency of conversion for each varies dramatically, and independently, between tissues. At one site, a highly conserved isoleucine in the seventh transmembrane span can be converted to a valine, a change that shifts the pump's intrinsic voltage dependence. Mechanistically, the removal of a single methyl group specifically targets the process of Na(+) release to the extracellular solution, causing a higher turnover rate at the resting membrane potential.
Institute of Neurobiology, University of Puerto Rico-Medical Sciences Campus, San Juan, Puerto Rico.
Claudia
C
Colina
Juan Pablo
JP
Palavicini
Deepa
D
Srikumar
Miguel
M
Holmgren
Joshua J C
JJ
Rosenthal
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D049832:Decapodiformes; D008969:Molecular Sequence Data; D021381:Protein Transport; D017393:RNA Editing; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D000254:Sodium-Potassium-Exchanging ATPase