440 kD
ankyrin-B and 480/270 kD
ankyrin-G are membrane skeletal
proteins with closely related biochemical properties yet distinctive physiological roles in axons. These
proteins associate with
spectrin-actin networks and also bind to
integral membrane proteins including the L1 CAM family of
cell adhesion molecules and
voltage-gated sodium channels. 440 kD
ankyrin-B is expressed with L1 in premyelinated axon tracts, and is essential for survival of these axons, at least in the case of the optic nerve. 440
ankyrin-B may collaborate with L1 in transcellular structures that mediate axon fasciculation and mechanically stabilize axon bundles, although these
proteins may also be involved in axon pathfinding.
Ankyrin-B (-/-) mice exhibit loss of L1 from premyelinated axon tracts and a similar, although much more severe, phenotype to L1 (-/-) mice and humans with L1 mutations.
Ankyrin-B and L1 thus are candidates to collaborate in the same structural pathway and defects in this pathway can lead to
nervous system malformations and
mental retardation. 480/270 kD
ankyrin-G are highly concentrated along with the
L1CAM family members neurofascin and NrCAM at nodes of Ranvier and axon initial segments.
Voltage-gated sodium channels bind directly to
ankyrins, and are likely to associate in a ternary complex containing neurofascin/NrCAM, and
ankyrin-G. Mice with
ankyrin-G expression abolished in the cerebellum exhibit loss of ability of Purkinje neurons to fire action potentials, as well as loss of restriction of neurofascin/NrCAM to axon initial segments.
Ankyrin-G thus is a key component in assembly of functional components of the axon initial segment and possibly the node of Ranvier.