title: Caveolin interaction governs Kv1.3 lipid raft targeting.
abstract: The spatial localization of ion channels at the cell surface is crucial for their functional role. Many channels localize in lipid raft microdomains, which are enriched in cholesterol and sphingolipids. Caveolae, specific lipid rafts which concentrate caveolins, harbor signaling molecules and their targets becoming signaling platforms crucial in cell physiology. However, the molecular mechanisms involved in such spatial localization are under debate. Kv1.3 localizes in lipid rafts and participates in the immunological response. We sought to elucidate the mechanisms of Kv1.3 surface targeting, which govern leukocyte physiology. Kv1 channels share a putative caveolin-binding domain located at the intracellular N-terminal of the channel. This motif, lying close to the S1 transmembrane segment, is situated near the T1 tetramerization domain and the determinants involved in the Kvβ subunit association. The highly hydrophobic domain (FQRQVWLLF) interacts with caveolin 1 targeting Kv1.3 to caveolar rafts. However, subtle variations of this cluster, putative ancillary associations and different structural conformations can impair the caveolin recognition, thereby altering channel's spatial localization. Our results identify a caveolin-binding domain in Kv1 channels and highlight the mechanisms that govern the regulation of channel surface localization during cellular processes.
authors.affiliation: Molecular Physiology Laboratory, Universitat de Barcelona, 08028 Barcelona, Spain.|Institut de Biomedicina (IBUB). Departament de Bioquímica i Biologia Molecular. Universitat de Barcelona, 08028 Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Pérez-Verdaguer
authors.affiliation: Molecular Physiology Laboratory, Universitat de Barcelona, 08028 Barcelona, Spain.|Institut de Biomedicina (IBUB). Departament de Bioquímica i Biologia Molecular. Universitat de Barcelona, 08028 Barcelona, Spain.
authors.forename: Jesusa
authors.initials: J
authors.lastname: Capera
authors.affiliation: Molecular Physiology Laboratory, Universitat de Barcelona, 08028 Barcelona, Spain.|Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Ramón
authors.initials: R
authors.lastname: Martínez-Mármol
authors.affiliation: Institut de Biomedicina (IBUB). Departament de Bioquímica i Biologia Molecular. Universitat de Barcelona, 08028 Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Camps
authors.affiliation: Molecular Physiology Laboratory, Universitat de Barcelona, 08028 Barcelona, Spain.|Departament Ciències Fisiològiques I, Universitat de Barcelona, 08036 Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Comes
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Tamkun
authors.affiliation: Molecular Physiology Laboratory, Universitat de Barcelona, 08028 Barcelona, Spain.|Institut de Biomedicina (IBUB). Departament de Bioquímica i Biologia Molecular. Universitat de Barcelona, 08028 Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Felipe
mesh_terms: D000595:Amino Acid Sequence; D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D022461:Caveolins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051664:Kv1.3 Potassium Channel / Q000737:chemistry / Q000378:metabolism*; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D001704:Biopolymers; D022461:Caveolins; D051664:Kv1.3 Potassium Channel