Ivanovic et al. report that a glial cytoskeletal adaptor protein organizes the membranes of Schwann cells and the axons they ensheath.
The speed of myelinated nerve conduction is boosted by the precise accumulation of ion channels in distinct membrane domains along the axon. Sodium channels, for example, accumulate in the nodes of Ranvier between neighboring Schwann cells, whereas potassium channels cluster on either side of the node, as well as between the nodes in a region of the axonal membrane adjacent to a seam in the surrounding myelin sheath termed the juxtamesaxonal line. Domain formation is dictated by distinct adhesion molecules in the membranes of both Schwann cells and axons, though how potassium channels localize to the juxtamesaxonal line is unknown.
Ivanovic et al. analyzed mice lacking 4.1G, an adaptor protein expressed in Schwann cells that links membrane proteins to the actin and spectrin cytoskeleton. In the absence of 4.1G, Schwann cell adhesion molecules such as Necl4 and NF155 were lost from the membrane contacting the underlying axon. As a result, several axonal membrane proteins were also mislocalized, including potassium channels, which aggregated and piled up near the nodes of Ranvier instead of stretching out along the juxtamesaxonal line.
Thus, in myelinating Schwann cells, 4.1G is required for the polarized distribution of proteins that in turn control the molecular organization of the internodal axonal membrane. Senior author Elior Peles now wants to investigate how the adaptor protein controls the expression levels and localization of Schwann cell adhesion molecules.