paranedes

Paranodes are specialized regions of myelinated axons located adjacent to the nodes of Ranvier. They form where the terminal loops of myelinating glia—oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system—encircle the axon and establish tight junctions with the axonal membrane. This arrangement helps anchor the myelin sheath to the axon and delineates the boundary between the node and the adjacent myelinated segments.

Molecularly, paranodes are organized by axon-glial adhesion complexes. The axonal proteins Caspr1 (CNTNAP1) and contactin-1 pair with the glial protein neurofascin NF155 to create septate-like junctions that tether the myelin loops to the axon at the paranodal region. This junctional architecture helps segregate nodal proteins from those in the juxtaparanodal region, where Kv1 family potassium channels reside, thereby maintaining distinct membrane domains.

Functionally, paranodes contribute to the stability of the node of Ranvier and restrict lateral diffusion of membrane proteins, supporting the precise localization of ion channels necessary for efficient saltatory conduction. They also participate in signaling between the axon and myelinating glia during development and in response to injury, enabling adaptive remodeling of the axonal membrane.

Clinical relevance is seen when paranodal integrity is compromised. Disruption of paranodal junctions is associated with demyelinating diseases such as multiple sclerosis and certain inherited neuropathies, leading to mislocalization of ion channels and impaired conduction velocity or block. Understanding paranodes aids in elucidating mechanisms of nerve function and disease.

See also: node of Ranvier; myelin; saltatory conduction; Schwann cell; oligodendrocyte; neurofascin; CNTNAP1.