On Tuesday morning, I attended the minisymposium on the Functional Organization of Plasma Membranes, organized by Matthew Rasband (Baylor College of Medicine, Houston) and the absent-due-to-illness Benedicte Dargent (Universitee de la Mediterranee).
Meanwhile, Bettina Winckler, from the University of Virginia, is interested in how a cell adhesion molecule called Neurofascin is specifically localized to the AIS, and nowhere else along the axon. Voltage-gated sodium channels are specifically targeted to the AIS through a combination of retention by binding to ankyrin, and endocytic removal from other membrane domains (see Fache et al, 2004). Winckler showed that a similar mechanism is used to accumulate Neurofascin at the AIS, although with a twist: Neurofascin doesn't bind directly to the clathrin endocytic machinery, but NGF signaling promotes its association with a protein that links the cell adhesion molecule to clathrin cargo adaptors. NGF therefore enhances Neurofascin's endocytosis from sites along the axon and dendrites, promoting its unique accumulation at the AIS, where it stably binds ankyrin and isn't internalized.