Sumoylation silences the plasma membrane leak K+ channel K2P1.
Reversible, covalent modification with small ubiquitin-related modifier proteins (SUMOs) is known to mediate nuclear import/export and activity of transcription factors. Here, the SUMO pathway is shown to operate at the plasma membrane to control ion channel function. SUMO-conjugating enzyme is seen to be resident in plasma membrane, to assemble with K2P1, and to modify K2P1 lysine 274. K2P1 had not previously shown function despite mRNA expression in heart, brain, and kidney and sequence features like other two-P loop K+ leak (K2P) pores that control activity of excitable cells. Removal of the peptide adduct by SUMO protease reveals K2P1 to be a K+-selective, pH-sensitive, openly rectifying channel regulated by reversible peptide linkage.
Rajan
Sindhu
S
Department of Pediatrics, Institute for Molecular Pediatric Sciences, Pritzker School of Medicine, University of Chicago, 5721 South Maryland Avenue, Chicago, Illinois 60637, USA.
Plant
Leigh D
LD
Rabin
Michael L
ML
Butler
Margaret H
MH
Goldstein
Steve A N
SA
D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism* / Q000502:physiology; D002522:Chlorocebus aethiops; D003546:Cysteine Endopeptidases; D004594:Electrophysiology; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D010455:Peptides / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000502:physiology*; D011485:Protein Binding; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis
D010455:Peptides; D024683:Potassium Channels, Tandem Pore Domain; D025841:Small Ubiquitin-Related Modifier Proteins; D029867:Xenopus Proteins; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases