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: After injury, myelin and nonmyelin (Remak) Schwann cells undergo a c-Jun–dependent reprogramming to form repair Schwann cells (Arthur-Farraj et al., 2012). We examined whether this important cell type conversion was altered in Atg7 cKO nerves using global proteomic analysis. Injury (5 d cut nerves) resulted in substantial changes in the proteomic profile, involving both up- and down-regulation (Fig. S4 E), as described previously (Jiménez et al., 2005). Notably, we found that 12 of the 25 most strongly down-regulated proteins after nerve cut in WT nerves were down-regulated to a significantly lesser degree in Atg7 cKO mice (Fig. 5 A). Conversely, 11 of the 25 most strongly up-regulated proteins in WT nerves were up-regulated to a significantly lesser degree in Atg7 cKO mice (Fig. 5 B). To further confirm that generation of repair Schwann cells was affected in the Atg7 cKO mice, we examined expression of markers associated with these cells after injury (Arthur-Farraj et al., 2012). We found that the expression of p75NTR protein, and of the Shh, GDNF, and Olig1 genes, was significantly reduced in the Atg7 cKO mice (Fig. 5, C and D).
Affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.