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 tar get proteins to axons, we assessed whether any of the large cytoplasmic reg ions of neuronal sodium channel Na(v)1.2 contain sufficient information for axonal compartmentalization. We show that addition of the cytoplasmic C-te rminal region of Na(v)1.2 restricted the distribution of a dendritic-axonal reporter protein to axons. The analysis of mutants revealed that a critica l segment of nine amino acids encompassing a di-leucine-based motif mediate s axonal compartmentalization of chimera. In addition, the Na(v)1.2 C-termi nus is recognized by the clathrin endocytic pathway both in non-neuronal ce lls and the somatodendritic domain of hippocampal neurons. The mutation of the di-leucine motif located within the nine amino acid sequence to alanine s resulted in the loss of chimera compartmentalization in axons and of inte rnalization. These data suggest that selective elimination by endocytosis i n dendrites may account for the compartmentalized distribution of some prot eins in axons.