Abstract
Schwann cell development and peripheral nerve myelination are finely orchestrated multistep processes; some of the underlying mechanisms are well described and others remain unknown. Many posttranslational modifications (PTMs) like phosphorylation and ubiquitination have been reported to play a role during the normal development of the peripheral nervous system (PNS) and in demyelinating neuropathies. However, a relatively novel PTM, SUMOylation, has not been studied in these contexts. SUMOylation involves the covalent attachment of one or more small ubiquitin-like modifier (SUMO) proteins to a substrate, which affects the function, cellular localization, and further PTMs of the conjugated protein. SUMOylation also regulates other proteins indirectly by facilitating non-covalent protein–protein interaction via SUMO interaction motifs (SIM). This pathway has important consequences on diverse cellular processes, and dysregulation of this pathway has been reported in several diseases including neurological and degenerative conditions. In this article, we revise the scarce literature on SUMOylation in Schwann cells and the PNS, we propose putative substrate proteins, and we speculate on potential mechanisms underlying the possible involvement of this PTM in peripheral myelination and neuropathies.
Highlights
Other reports describe important physiological and pathological roles for ubiquitination: it is involved in the maintenance of Schwann cell homeostasis, and it is dysregulated in demyelinating peripheral neuropathies [5]
Given the role of Krox20/NGFI-A binding (Nab) in the progression from promyelinating Schwann cells into myelination, we are tempted to speculate that failure of Krox20-mediated SUMOylation of Nab proteins might result in the arrest of Schwann cells in a proliferative stage and consequent peripheral neuropathy
We propose that the role of Rac1 in the formation of radial lamellipodia in Schwann cells could be regulated by SUMOylation, an exciting hypothesis that warrants further investigation
Summary
Our knowledge regarding the functional significance of SUMOylation in myelinating glia is very limited, these targets are promising candidates that may be regulated by SUMO modification in Schwann cells, impacting on crucial mechanisms of differentiation, radial sorting, myelin formation, and/or maintenance. Similar to other PTMs, SUMOylation is a dynamic and reversible process with deSUMOylation performed by SUMO-specific proteases (SENPs, Figure 1) These enzymes are involved in the maturation of precursors and the edition of Sumo2/3 chains.
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