Figure 1.

A) Domain organization of the axon with axon initial segments (regions B and C) and nodes of Ranvier (region D).

B) Sorting of axonal and dendritic cargoes is a microtubule-dependent mechanism. Recent studies have shown that TRIM46 is found at and just proximal to the AIS (right) and is responsible for the bundling of microtubules. The dynein regulator NDEL1 is also important for sorting of vesicles and functions to exclude vesicles from the AIS. Scale bar = 10 µm.

C) The actin/spectrin/ankyrin submembranous cytoskeleton is organized as a periodic lattice of proteins that alternate between actin rings and spectrin/ankyrin complexes. STORM super-resolution imaging has given this unprecedented level of structural and molecular detail (right). Immunostaining pictures from [10].

D) Two cytoskeleton-dependent mechanisms are responsible for ion channel clustering at nodes of Ranvier: an active clustering mechanism mediated by a hierarchy of ankyrins and spectrins, and a paranodal exclusion barrier mediated by αII and βII spectrin. In nodes lacking ankG, ankR and βI spectrin compensate for the loss of ankG and βIV spectrin. Adapted from [1].