Schwannomas provide insight into the role of p75(NTR) and merlin in Schwann cells following nerve injury and during regeneration.

Abstract

Peripheral nerve injury leads to Wallerian degeneration of severed axons, leaving the Schwann cell (SC) sheath behind. Denervated SCs may then either survive and remyelinate a regenerating axon, or they may undergo cell death. Because SCs provide trophic support and guidance cues to regenerating nerve fibers, SC loss severely hampers nerve regeneration (Hall, 1986). Thus, significant work has sought to characterize the molecular mechanisms underlying SC fate following peripheral nerve injury. A deeper understanding of these mechanisms has recently been derived from a somewhat unexpected source; cell survival signaling in benign schwannoma tumors has yielded insight into survival signaling in denervated SCs. This recent evidence implicates a pathway involving the single transmembrane neurotrophin receptor p75NTR and Moesin-ezrin-radixin-like protein (merlin, also known as schwannomin or neurofibromin 2), a membrane-cytoskeleton scaffolding protein linking the cellular membrane to the actin cytoskeleton.