RGD Reference Report - Kv1.5 association modifies Kv1.3 traffic and membrane localization. - Rat Genome Database

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Kv1.5 association modifies Kv1.3 traffic and membrane localization.

Authors: Vicente, R  Villalonga, N  Calvo, M  Escalada, A  Solsona, C  Soler, C  Tamkun, MM  Felipe, A 
Citation: Vicente R, etal., J Biol Chem. 2008 Mar 28;283(13):8756-64. doi: 10.1074/jbc.M708223200. Epub 2008 Jan 24.
RGD ID: 8554598
Pubmed: PMID:18218624   (View Abstract at PubMed)
PMCID: PMC2417174   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M708223200   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kcna3Ratmembrane raft located_inIDA PMID:18218624BHF-UCL 
Kcna3Ratplasma membrane located_inIDA PMID:18218624BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Kcna3  (potassium voltage-gated channel subfamily A member 3)

Additional Information