Abstract

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.

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