A novel targeting signal for proximal clustering of the Kv2.1 K+ channel in hippocampal neurons.
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.
Lim
S T
ST
Department of Biochemistry and Cell Biology and Institute for Cell and Developmental Biology, State University of New York, Stony Brook 11794, USA.
Antonucci
D E
DE
Scannevin
R H
RH
Trimmer
J S
JS
D000595:Amino Acid Sequence; D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D010446:Peptide Fragments / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D017434:Protein Structure, Tertiary; D017966:Pyramidal Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051669:Shab Potassium Channels; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
D051668:Delayed Rectifier Potassium Channels; C496991:Kcnb1 protein, rat; C496994:Kcnb2 protein, rat; D008565:Membrane Proteins; D010446:Peptide Fragments; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D051669:Shab Potassium Channels