Abstract

Peripheral nerves have the capacity to conduct action potentials along great distances and quickly recover following damage which is mainly due to Schwann cells (SCs), the most abundant glial cells of the peripheral nervous system (PNS). SCs wrap around an axonal segment multiple times, forming a myelin sheath, allowing for a significant increase in action potential conduction by insulating the axons. Mature myelin consists of compact and non-compact (or cytoplasmic) myelin zones. Non-compact myelin is found in paranodal loops bordering the nodes of Ranvier, and in the inner and outermost cytoplasmic tongues and is the region in which Schmidt-Lanterman incisures (SLI; continuous spirals of overlapping cytoplasmic expansions within areas of compact myelin) are located. Using different technologies, it was shown that the layers of non-compact myelin could be connected to each other by gap junction channels (GJCs), formed by connexin 32 (Cx32), and their relative abundance allows for the transfer of ions and different small molecules. Likewise, Cx29 is expressed in the innermost layer of the myelin sheath. Here it does not form GJCs but colocalizes with Kv1, which implies that the SCs play an active role in the electrical condition in mammals. The critical role of GJCs in the functioning of myelinating SCs is evident in Charcot-Marie-Tooth disease (CMT), X-linked form 1 (CMTX1), which is caused by mutations in the gap junction protein beta 1 (GJB1) gene that codes for Cx32. Although the management of CMT symptoms is currently supportive, there is a recent method for targeted gene delivery to myelinating cells, which rescues the phenotype in KO-Cx32 mice, a model of CMTX1. In this mini-review article, we discuss the current knowledge on the role of Cxs in myelin-forming SCs and summarize recent discoveries that may become a real treatment possibility for patients with disorders such as CMT.

Highlights

  • Peripheral nerves have the capacity to conduct action potentials along great distances and quickly recover following damage which is mainly due to Schwann cells (SCs), the most abundant glial cells of the peripheral nervous system (PNS)

  • It was shown that the layers of non-compact myelin could be connected to each other by gap junction channels (GJCs), formed by connexin 32 (Cx32), and their relative abundance allows for the transfer of ions and different small molecules

  • The critical role of GJCs in the functioning of myelinating SCs is evident in Charcot-Marie-Tooth disease (CMT), X-linked form 1 (CMTX1), which is caused by mutations in the gap junction protein beta 1 (GJB1) gene that codes for Cx32

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Summary

MYELINATING SCHWANN CELLS

The ability of peripheral nerves to recover quickly after damage is mostly due to the plasticity of Schwann cells (SCs; Boerboom et al, 2017). SCs are the principal glia of the peripheral nervous system (PNS; Fehmi et al, 2018). In the development of vertebrate PNS, SCs are derived from neural crest cells that differentiate into SC precursors and into immature SCs (Jessen and Mirsky, 2005; Boerboom et al, 2017). The process of myelination begins around birth, where SCs cover axons that are larger than ∼1 μm in diameter (Fehmi et al, 2018)

Schwann Cells and Connexins
THE ISSUE OF INTRACELLULAR COMMUNICATION IN MYELINATED SCHWANN CELLS
GAP JUNCTION CHANNELS IN MYELINATING SCHWANN CELLS
DISEASES ASSOCIATED WITH DYSFUNCTION OF CONNEXINS IN SCHWANN CELLS
Findings
CONCLUSIONS
Full Text
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