Physiological roles of axonal ankyrins in survival of premyelinated axons and localization of voltage-gated sodium channels.
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.
Bennett
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Howard Hughes Medical Institute and Departments of Cell Biology and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
Lambert
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D000818:Animals; D017487:Ankyrins / Q000502:physiology*; D001369:Axons / Q000737:chemistry / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D015222:Sodium Channels / Q000378:metabolism*
D017487:Ankyrins; D015222:Sodium Channels