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Identification of an axonal determinant in the C-terminus of the sodium channel Na(v)1.2

To obtain a better understanding of how hippocampal neurons selectively target proteins to axons, we assessed whether any of the large cytoplasmic regions of neuronal sodium channel Na(v)1.2 contain sufficient information for axonal compartmentalization. We show that addition of the cytoplasmic C-te...

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Published in:The EMBO journal 2001-11, Vol.20 (21), p.5950
Main Authors: Garrido, J J, Fernandes, F, Giraud, P, Mouret, I, Pasqualini, E, Fache, M P, Jullien, F, Dargent, B
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container_title The EMBO journal
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creator Garrido, J J
Fernandes, F
Giraud, P
Mouret, I
Pasqualini, E
Fache, M P
Jullien, F
Dargent, B
description To obtain a better understanding of how hippocampal neurons selectively target proteins to axons, we assessed whether any of the large cytoplasmic regions of neuronal sodium channel Na(v)1.2 contain sufficient information for axonal compartmentalization. We show that addition of the cytoplasmic C-terminal region of Na(v)1.2 restricted the distribution of a dendritic-axonal reporter protein to axons. The analysis of mutants revealed that a critical segment of nine amino acids encompassing a di-leucine-based motif mediates axonal compartmentalization of chimera. In addition, the Na(v)1.2 C-terminus is recognized by the clathrin endocytic pathway both in non-neuronal cells and the somatodendritic domain of hippocampal neurons. The mutation of the di-leucine motif located within the nine amino acid sequence to alanines resulted in the loss of chimera compartmentalization in axons and of internalization. These data suggest that selective elimination by endocytosis in dendrites may account for the compartmentalized distribution of some proteins in axons.
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subjects Amino Acid Motifs - physiology
Amino Acid Sequence
Animals
Axons - metabolism
Cell Compartmentation - physiology
Cells, Cultured
COS Cells
Dendrites - metabolism
Genes, Reporter
HeLa Cells
Hippocampus - cytology
Hippocampus - metabolism
Humans
Molecular Sequence Data
Mutagenesis, Site-Directed
NAV1.2 Voltage-Gated Sodium Channel
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neurons - cytology
Neurons - metabolism
Protein Transport - physiology
Rats
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Sodium Channels - genetics
Sodium Channels - metabolism
Structure-Activity Relationship
title Identification of an axonal determinant in the C-terminus of the sodium channel Na(v)1.2
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