Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 842K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?

No endocytosis in the axonal entry

AIS proteins (green) are internalized everywhere except the AIS.

It takes two steps to localize a sodium channel to its proper location at the entrance to the axon, based on results on page 571 from Fache et al. Their findings are consistent with a targeting system involving both tethering and selective elimination.

The boundary between the neuronal cell body and the axon, called the axonal initial segment (AIS), is a dense network of actin and ankyrin G and ß IV spectrin, where clusters of sodium channels initiate action potentials. A cytoplasmic loop from the Na_v1.2 sodium channel binds to ankyrin and, when added to non-AIS proteins, can direct them to this segment. The authors now show that this loop contains two separate domains essential for precise localization.

One domain tethers the protein to ankyrin, and the other removes it from surface of the rest of the neuron. Mutation of the first domain—a 27-residue stretch that binds to ankyrin—caused chimeric proteins with the mutant loop to localize throughout the cell.

A nearby but nonoverlapping domain was also needed to limit protein localization to the AIS by removing proteins from the surface elsewhere. Newly made chimeric proteins were sent to the plasma membrane all around the cell body, including the AIS. Those that did not land at or move to the AIS were then internalized, as were proteins that somehow found their way to the far end of the axon. Removal of 19 residues in the NH₂-terminal portion of the loop abolished this endocytosis, and protein accumulated throughout the neuron.

It is not clear what prevents the endocytosis in the AIS, although linkage to ankyrin does not seem to be necessary. Perhaps endocytosis is generally limited in the AIS. The NH₂-terminal portion of the loop is unlike any known internalization sequence and should provide a good starting point to identify proteins needed for this endocytic pathway.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Full Text (PDF, 842K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?