regulation of na+k+ atpase transport velocity by rna editingna + k + atp酶的监管运输速度通过rna编辑.pdfVIP

+ + Regulation of Na /K ATPase Transport Velocity by RNA Editing 1 1 2 2 1,3 Claudia Colina , Juan Pablo Palavicini , Deepa Srikumar , Miguel Holmgren *, Joshua J. C. Rosenthal * 1 Institute of Neurobiology, University of Puerto Rico–Medical Sciences Campus, San Juan, Puerto Rico, 2 Molecular Neurophysiology Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America, 3 Department of Biochemistry, University of Puerto Rico–Medical Sciences Campus, San Juan, Puerto Rico Abstract + + 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