The role of gangliosides in the organisation of the node of Ranvier examined in glycosyltransferase transgenic mice.

Rhona McGonigal,Hugh J. Willison

doi:10.1111/joa.13562

Abstract

Gangliosides are a family of sialic acid containing glycosphingolipids highly enriched in plasma membranes of the vertebrate nervous system. They are functionally diverse in modulating nervous system integrity, notably at the node of Ranvier, and also act as receptors for many ligands including toxins and autoantibodies. They are synthesised in a stepwise manner by groups of glycosyl‐ and sialyltransferases in a developmentally and tissue regulated manner. In this review, we summarise and discuss data derived from transgenic mice with different transferase deficiencies that have been used to determine the role of glycolipids in the organisation of the node of Ranvier. Understanding their role at this specialised functional site is crucial to determining differential pathophysiology following directed genetic or autoimmune injury to peripheral nerve nodal or paranodal domains, and revealing the downstream consequences of axo‐glial disruption.

Highlights

Gangliosides are sialic acid containing glycosphingolipids widely expressed in vertebrate plasma membranes and intracellular compartments (Ledeen & Wu, 2011; Sandhoff & Harzer, 2013; Yu et al, 2011)
Whilst ganglioside biosynthesis and distribution is widespread throughout the body, the nervous system in particular is very highly enriched in complex gangliosides relative to other organs and tissues
We will focus our attention on the role of gangliosides in the maintenance of the mammalian node of Ranvier (NoR), a specialised membrane domain formed by myelin-forming cells: Schwann cells in the PNS and oligodendrocytes in the CNS (Figure 1)

Summary

| INTRODUCTION

Gangliosides are sialic acid containing glycosphingolipids widely expressed in vertebrate plasma membranes and intracellular compartments (Ledeen & Wu, 2011; Sandhoff & Harzer, 2013; Yu et al, 2011). The NoR appear to develop normally followed by subsequent generalised impairment of the paranodal axo–glial junction We advanced these studies to consider the compensatory roles of complex gangliosides and sulphatide in maintaining axo-glial stability at NoR by combining GalNAc-T −/− and CST −/− strains and examining the nodal phenotype (McGonigal et al, 2019). Whilst the above studies have indicated that complex gangliosides are required for nervous system maintenance, stability and repair including the NoR, it is unknown whether neuronal or glial ganglioside deficiency has the greater impact on the age-related phenotype and maintenance of the axon, myelin and axo-glial junction. The current immunohistological data demonstrate that the NoR are grossly normal in all of the lines studied at this age, thereby confirming their suitability for use in peripheral nerve injury models going forward

| CONCLUSION

Findings

| METHODS