Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves.
Bottom Line: Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury.We also present evidence that myelinophagy is defective in the injured central nervous system.These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease.
Affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.Show MeSH
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Mentions: Transcriptional regulation of autophagy-related genes coincides with autophagy induction in several systems (Klionsky et al., 2012). To examine whether autophagy is involved in myelin degradation, we analyzed expression of autophagy-related genes broadly classified into functional subgroups comprising the core autophagy machinery and its main regulators (Feng et al., 2014). Sciatic nerves were transected and the distal stump was analyzed over the time course of demyelination. We found a strong induction of several autophagy-related genes during demyelination, notably members of the ULK complex and Atg9 cycling system, and Atg7, all essential for autophagosome formation (Fig. 1 A and Fig. S1). Concurrent with the degradative decline of myelin proteins MPZ and MBP, we observed an increase, compared with uninjured levels, of several ATG proteins including ATG7, components of the ATG16L complex, Wipi2, and Beclin1 in injured nerves, which is consistent with a role for autophagy in Wallerian degeneration (Fig. 1 B; quantified in Fig. S2).
Affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.