Abstract
The discrete localization of ion channels is a critical determinant of neuronal excitability. We show here that the dendritic K+ channels Kv2.1 and Kv2.2 were differentially targeted in cultured hippocampal neurons. Kv2.1 was found in high-density clusters on the soma and proximal dendrites, while Kv2.2 was uniformly distributed throughout the soma and dendrites. Chimeras revealed a proximal restriction and clustering domain on the cytoplasmic tail of Kv2.1. Truncations and internal deletions revealed a 26-amino acid targeting signal within which four residues were critical for localization. This signal is not related to other known sequences for neuronal and epithelial membrane protein targeting and represents a novel cytoplasmic signal responsible for proximal restriction and clustering.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Polarity / physiology
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Cells, Cultured
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Delayed Rectifier Potassium Channels
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Epithelial Cells / chemistry
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Epithelial Cells / cytology
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Epithelial Cells / metabolism
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Fluorescent Antibody Technique
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Gene Expression / physiology
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Hippocampus / cytology
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Membrane Proteins / analysis
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Molecular Sequence Data
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Mutagenesis / physiology
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Peptide Fragments / analysis
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Point Mutation
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Potassium Channels / chemistry
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Potassium Channels / genetics
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Potassium Channels / metabolism*
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Potassium Channels, Voltage-Gated*
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Protein Structure, Tertiary
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Pyramidal Cells / chemistry
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Pyramidal Cells / cytology
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Pyramidal Cells / metabolism*
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Rats
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Recombinant Proteins / analysis
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Shab Potassium Channels
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Signal Transduction / physiology*
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Transfection
Substances
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Delayed Rectifier Potassium Channels
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Kcnb1 protein, rat
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Kcnb2 protein, rat
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Membrane Proteins
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Peptide Fragments
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Potassium Channels
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Potassium Channels, Voltage-Gated
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Recombinant Proteins
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Shab Potassium Channels