title: Kv1.5 association modifies Kv1.3 traffic and membrane localization.
abstract: Kv1.3 activity is determined by raft association. In addition to Kv1.3, leukocytes also express Kv1.5, and both channels control physiological responses. Because the oligomeric composition may modify the channel targeting to the membrane, we investigated heterotetrameric Kv1.3/Kv1.5 channel traffic and targeting in HEK cells. Kv1.3 and Kv1.5 generate multiple heterotetramers with differential surface expression according to the subunit composition. FRET analysis and pharmacology confirm the presence of functional hybrid channels. Raft association was evaluated by cholesterol depletion, caveolae colocalization, and lateral diffusion at the cell surface. Immunoprecipitation showed that both Kv1.3 and heteromeric channels associate with caveolar raft domains. However, homomeric Kv1.3 channels showed higher association with caveolin traffic. Moreover, FRAP analysis revealed higher mobility for hybrid Kv1.3/Kv1.5 than Kv1.3 homotetramers, suggesting that heteromers target to distinct surface microdomains. Studies with lipopolysaccharide-activated macrophages further supported that different physiological mechanisms govern Kv1.3 and Kv1.5 targeting to rafts. Our results implicate the traffic and localization of Kv1.3/Kv1.5 heteromers in the complex regulation of immune system cells.
authors.affiliation: Molecular Physiology Laboratory, Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Vicente
authors.forename: Núria
authors.initials: N
authors.lastname: Villalonga
authors.forename: Maria
authors.initials: M
authors.lastname: Calvo
authors.forename: Artur
authors.initials: A
authors.lastname: Escalada
authors.forename: Carles
authors.initials: C
authors.lastname: Solsona
authors.forename: Concepció
authors.initials: C
authors.lastname: Soler
authors.forename: Michael M
authors.initials: MM
authors.lastname: Tamkun
authors.forename: Antonio
authors.initials: A
authors.lastname: Felipe
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004594:Electrophysiology; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D051666:Kv1.5 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats
chemical_list: D051664:Kv1.3 Potassium Channel; D051666:Kv1.5 Potassium Channel