Figure 2.

Distinct voltage-dependent K⁺ channel compositions trigger different membrane surface microdomain targeting. While Kv1.3 efficiently targets to lipid rafts (a), Kv1.5 targeting depends on partnership interactions. Kv1.5 localizes in rafts when overexpressed in heterologous systems (b). However, the channel does not target to these microdomains in native tissues, probably due to the presence of interacting subunits yet to determine (e.g., Kvβ2.1) (c). In leukocytes, heterotetrameric channels with high Kv1.3/Kv1.5 (Kv1.3/Kv1.5) ratio localize in rafts (d). On the contrary, low Kv1.3/Kv1.5 ratios (↓Kv1.3/Kv1.5) impair raft localization of the channels (e). Macrophage activation, which triggers a selective increase of Kv1.3 subunits, generates high Kv1.3/Kv1.5 ratio heteromers which target back to lipid rafts (f).