One of the long-term research goals of our laboratory is to elucidate the molecular mechanisms involved in subcellular localization of voltage-gated K+ channels. We hypothesize that the peptide sequences of K+ channels contain amino acid motifs that target them to distinct neuronal compartments. Understanding the subcellular localization mechanisms for K+ channels is important because disruption of K+ channel function has been associated with susceptibility to epileptic seizures. In addition, amyloid precursor protein (APP), which has been implicated in Alzheimer's disease, has been found to play a role in axonal transport. Thus, disruption of transport mechanisms results in pathology. To identify targeting motifs, we will use chimeras between two channels that differentially localize, and perform alignments with similar localizing channels. We will use biolistic transfection of cultured brain slices as our experimental system which we will visualize using confocal microscopy.
The specific aims are:
Aim 1). To identify an amino acid motif that is necessary and sufficient for somatodendritic targeting of Kv4.2.
and Aim 2). To identify the amino acid motif that is necessary and sufficient for axonal targeting of the Kv1.3 channel.
| Rivera, Jacqueline; Chu, Po-Ju; Lewis Jr, Tommy L et al. (2007) The role of Kif5B in axonal localization of Kv1 K(+) channels. Eur J Neurosci 25:136-46 |
