Regulation of differentiation and proliferation of Schwann cells is an essential part of the regulation of peripheral nerve development, degeneration, and regeneration. ZNRF1, a ubiquitin ligase, is expressed in undifferentiated/repair Schwann cells, directs glutamine synthetase to proteasomal degradation, and thereby increase glutamate levels in Schwann cell environment. Glutamate elicits subcellular signaling in Schwann cells via mGluR2 to modulate Neuregulin-1/ErbB2/3 signaling and thereby promote undifferentiated phenotype of Schwann cell.
Keywords: Differentiation; ErbB2/3; Glutamate; Neuregulin-1; Oxidative stress; Phosphorylation; Subcellular signaling; ZNRF1 ubiquitin ligase; mGluR2.