SIDL interacts with the dendritic targeting motif of Shal (K(v)4) K+ channels in Drosophila.

Shal K(+) (K(v)4) channels in mammalian neurons have been shown to be localized exclusively to somato-dendritic regions of neurons, where they function as key determinants of dendritic excitability. To gain insight into the mechanisms underlying dendritic localization of K(v)4 channels, we use Drosophila melanogaster as our model system. We show that Shal K(+) channels display a conserved somato-dendritic localization in vivo in Drosophila. From a yeast-2-hybrid screen, we identify the novel interactor, SIDL (for Shal Interactor of Di-Leucine Motif), as the first target protein reported to bind the highly conserved di-leucine motif (LL-motif) implicated in dendritic targeting. We show that SIDL is expressed primarily in the nervous system, co-localizes with GFP-Shal channels in neurons, and interacts specifically with the LL-motif of Drosophila and mouse Shal channels. We disrupt the Shal-SIDL interaction by mutating the LL-motif on Shal channels, and show that Shal K(+) channels are then mislocalized to some, but not all, axons in vivo. These results suggest that there are multiple mechanisms underlying Shal K(+) channel targeting, one of which depends on the LL-motif. The identification of SIDL may provide the first step for future investigation into the molecular machinery regulating the LL-motif-dependent targeting of K(+) channels.