The acetylome of adult mouse sciatic nerve.

Lysine acetylation is a reversible post-translational modification (PTM) involved in multiple physiological functions. Recent studies have demonstrated the involvement of protein acetylation in modulating the biology of Schwann cells (SCs) and regeneration of the peripheral nervous system (PNS). However, the mechanisms underlying these processes remain partially understood. Here, we characterized the acetylome of the mouse sciatic nerve (SN) and investigated the cellular distribution of acetylated proteins. We identified 483 acetylated proteins containing 1442 acetylation modification sites in the SN of adult C57BL/6 mice. Bioinformatics suggested that these acetylated SN proteins were mainly located in the myelin sheath, mitochondrial inner membrane, and cytoskeleton, and highlighted the significant differences between the mouse SN and brain acetylome. Manual annotation further indicated that most acetylated proteins (> 45%) were associated with mitochondria, energy metabolism, and cytoskeleton and cell adhesion. We verified three newly discovered acetylation-modified proteins, including neurofilament light polypeptide (NEFL), neurofilament medium/high polypeptide (NFM/H), and periaxin (PRX). Immunofluorescence illustrated that the acetylated proteins, including acetylated alpha-tubulin, were mainly co-localized with S100-positive SCs. Herein, we provided a comprehensive acetylome for the mouse SN and demonstrated that acetylated proteins in the SN were predominantly located in SCs. These results will extend our understanding and promote further study of the role and mechanism of protein acetylation in SC development and PNS regeneration.

Semaphorin 3E promote Schwann cell proliferation and migration.

Schwann cells (SCs) play a critical role in peripheral nerve (PN) regeneration because of their ability to proliferate, migrate, and provide trophic support for axon regeneration after PN injury. However, the underlying mechanism is still partially understood. Semaphorin3E (Sema3E), a member of the Sema3s family, is a secreted molecular known as a repelling cue in axon guidance and inhibitor of developmental and postischemic angiogenesis. In this study, we examined the expression of Sema3E in sciatic nerves and SCs and explored the effects of Sema3E on SCs proliferation and migration. Immunofluorescence and ELISA analyses illustrated the expression of Sema3E in SCs of Sciatic nerves and the secretion of Sema3E by cultured SCs, respectively. Exogenous Sema3E promoted SC proliferation and migration while knockdown of the endogenous Sema3E by siRNA transfection attenuated proliferation and migration of SCs. Furthermore, blocking the receptor Neuropilin 1 (Nrp1), PlexinD1 and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) by neutralizing antibody or inhibitor suppressed the promoting effects of Sema3E on SCs. This study indicated that Sema3E promoted SC proliferation and migration and the involvement of receptor PlexinD1, Nrp1, and VEGFR2 in these processes. This study extended our understanding of the mechanism that modulated SC phenotype during nerve injury and provided a potential target for promoting PN regeneration.