The making of a node: a co-production of neurons and glia

Abstract

Nodes of Ranvier are specialized axonal domains formed in response to a glial signal. Recent research advances have revealed that both CNS and PNS nodes form by several overlapping molecular mechanisms. However, the precise nature of these mechanisms and the hierarchy existing between them is considerably different in CNS versus PNS nodes. Namely, the Schwann cells of the PNS, which directly contact the nodal axolemma, secrete proteins that cluster axonodal components at the edges of the growing myelin segment. In contrast, the formation of CNS nodes, which are not contacted by the myelinating glia, is surprisingly similar to the assembly of the axon initial segment and depends largely on axonal diffusion barriers.

Figure 1

Current models for the formation of nodes and AIS. A-B. AIS and CNS nodes. The assembly of both the AIS and CNS nodes starts by the formation of a diffusion barrier marked by ankB and 4.1B. For nodes, this occurs at the base of the formed paranodal junction. In the adjacent AIS or nodal axolemma, accumulation of ankG results in the clustering of Nav and of NF186. ECM is the last to appear, and together with NF186, is probably required for the stabilization of AIS and nodal complexes. An asctrocyte process may contact CNS nodes late in development, although the exact timing is still to be determined. C. PNS nodes. The assembly of PNS nodes is induced by glial gliomedin and NrCAM that cluster NF186 on the axolemma, resulting in the accumulation of ankG and Nav. Linkage of the forming complex to the submembranous actin cytoskeleton likely occurs earlier in CNS nodes formation [26] and later in AIS and PNS nodes [7,26]. See table 1 for additional components not described here.