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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31GM070408-02
Application #
6896544
Study Section
Special Emphasis Panel (ZRG1-F05 (29))
Program Officer
Gaillard, Shawn R
Project Start
2004-06-01
Project End
2006-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
2
Fiscal Year
2005
Total Cost
$27,906
Indirect Cost
Name
University of Southern California
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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