FIGURE 4.

Schematics depicting the likely impact of increasing glycolipid deficiency on paranodal arrangement at nodes of Ranvier based on known data from the PNS and CNS. Particular focus is placed on the paranodal axo‐glial proteins Caspr, NF155 and MAG about which most is known. Lengthening of Nav channel domains are indicated by the pink arrow and invasion of juxtaparanodal Kv channels into the paranode suggestive of breakdown of the axo‐glial junction at the paranodal/juxtaparanodal border, by the green arrow. The transgenic lines represented by each stage of nodal organisation are defined below the relevant schematic, and age is also defined. In ganglioside deficient states, there is nodal lengthening, followed by Caspr/NF155 disturbance and Kv1.1 invasion into the lateral paranode. Normally GD1a and GT1b in rafts will tether MAG but in their absence, MAG does not make the axo‐glial connection. If NF155 is present, this protein can partner with Caspr/Contactin to make an axo‐glial junction. However, when sulphatide is absent, NF155 is also lost from the paranode. In the absence of NF155, Caspr presence is also diminished, and this is exacerbated with the additional loss of complex ganglioside rafts. Under both ganglioside and sulphatide raft deficiency, we propose that MAG and NF155 are both absent from the paranodal axo‐glial domain. This figure uses schematics modified from Figure 8, McGonigal et al., (2019) (https://doi.org/10.1523/JNEUROSCI.2095‐18.2018) with permission under the Creative Commons CC‐BY licence (http://creativecommons.org/licenses/by/4.0/)