title: Background K(2P) channels KCNK3/9/15 limit the budding of cell membrane-derived vesicles.
abstract: The main function of background two-pore potassium (K(2P)) channels KCNK3/9/15 is to stabilize the cell membrane potential. We previously observed that membrane potential depolarization enhances the release of HIV-1 viruses. Because membrane polarization affects the biomembrane directly, here we examined the effects of KCNK3/9/15 on the budding of nonviral vesicles. We found that depolarization by knocking down endogenous KCNK3/9/15 promoted secretion of cell-derived vesicles. We further used Vpu (an antagonist of KCNK3) as a model for the in vivo study of depolarization-stimulated secretion. Vpu is a HIV-1-encoded, ion channel-like protein (viroporin) capable of enhancing virus release and depolarizing the cell membrane potential. We found that Vpu could also promote nonviral vesicle release, perhaps through a similar mechanism that Vpu utilizes to promote viral particle release. Notably, T cells expressing Vpu alone became pathologically low in intracellular K(+) and insensitive to extracellular K(+) or membrane potential stimulation. In contrast, heterologous expression of KCNK3 in T cells stabilized the cell potentials by maintaining intracellular K(+). We thus concluded that KCNK3/9/15 expression limits membrane depolarization and depolarization-induced secretion at least in part by maintaining intracellular K(+).
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Tamsui 251, Taiwan.
authors.forename: Daniel Tsung-Ning
authors.initials: DT
authors.lastname: Huang
authors.forename: Naiwen
authors.initials: N
authors.lastname: Chi
authors.forename: Shiou-Ching
authors.initials: SC
authors.lastname: Chen
authors.forename: Ting-Ying
authors.initials: TY
authors.lastname: Lee
authors.forename: Kate
authors.initials: K
authors.lastname: Hsu
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D004161:Diphenylhexatriene / Q000031:analogs & derivatives / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D015497:HIV-1 / Q000502:physiology; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000494:pharmacology; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D020014:K562 Cells; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D054298:Human Immunodeficiency Virus Proteins; C431132:KCNK15 protein, human; C498655:KCNK9 protein, human; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D004161:Diphenylhexatriene; C420132:potassium channel subfamily K member 3; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene; D011188:Potassium