Rapid endocytosis provides restricted somatic expression of a K⁺ channel in central neurons

Trafficking motifs present in the intracellular regions of ion channels affect their subcellular location within neurons. The mechanisms that control trafficking to dendrites of central neurons have been identified, but it is not fully understood how channels are localized to the soma. We have now identified a motif within the calcium-activated potassium channel K_Ca2.1 (SK1) that results in somatic localization. Transfection of hippocampal neurons with K_Ca2.1 subunits causes expression of functional channels in only the soma and proximal processes. By contrast, expressed K_Ca2.3 subunits are located throughout the processes of transfected neurons. Point mutation of K_Ca2.1 within this novel motif to mimic a sequence present in the C-terminus of K_Ca2.3 causes expression of K_Ca2.1 subunits throughout the processes. We also demonstrate that blocking of clathrin-mediated endocytosis causes K_Ca2.1 subunit expression to mimic that of the mutated subunit. The role of this novel motif is therefore not to directly target trafficking of the channel to subcellular compartments, but to regulate channel location by subjecting it to rapid clathrin-mediated endocytosis.