A C-Terminal Domain Directs Kv3.3 Channels to Dendrites

Abstract

Pyramidal neurons of the electrosensory lateral line lobe (ELL) ofApteronotus leptorhynchusexpress Kv3-type voltage-gated potassium channels that give rise to high-threshold currents at the somatic and dendritic levels. Two members of the Kv3 channel family,AptKv3.1 andAptKv3.3, are coexpressed in these neurons.AptKv3.3 channels are expressed at uniformly high levels in each of four ELL segments, whereasAptKv3.1 channels appear to be expressed in a graded manner with higher levels of expression in segments that process high-frequency electrosensory signals. Immunohistochemical and recombinant channel expression studies show a differential distribution of these two channels in the dendrites of ELL pyramidal neurons.AptKv3.1 is concentrated in somas and proximal dendrites, whereasAptKv3.3 is distributed throughout the full extent of the large dendritic tree. Recombinant channel expression ofAptKv3 channels throughin vivoviral injections allowed directed retargeting ofAptKv3 subtypes over the somadendritic axis, revealing that the sequence responsible for targeting channels to distal dendrites lies within the C-terminal domain of theAptKv3.3 protein. The targeting domain includes a consensus sequence predicted to bind to a PDZ (postsynaptic density-95/Discs large/zona occludens-1)-type protein–protein interaction motif. These findings reveal that different functional roles for Kv3 potassium channels at the somatic and dendritic level of a sensory neuron are attained through specific targeting that selectively distributes Kv3.3 channels to the dendritic compartment.