UC San Diego

In rats, myelination begins at birth and continues for 1-2 weeks of development. Schwann cells (SCs) form myelin and insulate large-diameter axons in order to promote saltatory conduction and maintain axonal integrity. After injury in adults, SCs promote transcription of regeneration-associated genes and downregulate myelin program to generate repair SCs. The LRP1 receptor is upregulated after injury and is important to the SC repair program, but the roles of LRP1 during developmental myelination are unknown.

To establish the relationship between LRP1 and myelination, changes in LRP1 gene expression were analyzed over the course of development and in myelinating SCs in vitro. An in vitro model of developmental myelination was established from primary rat SCs, as confirmed by upregulation of the myelin marker proteins MBP and P0 and downregulation of p75NTR. LRP1 expression was downregulated after differentiation in vitro. Phosphoprotein analysis showed differentiation reduced activation of c-Jun, increased activation of Akt, and did not change activation of ERK1/2. Differentiation also reduced activation of ERK1/2 signaling in response to NRG1 and the LRP1 ligand α2M*, and furthermore impaired the ability of SCs to internalize myelin debris by phagocytosis.

These results indicate that LRP1 expression is inversely associated with myelination and is expressed by non-myelinating SCs. Future experiments should be done to reveal the mechanisms of and response to signaling in non-myelinating SCs during development. Additionally, in the future we may generate repair SCs in vitro to test novel roles for LRP1 during repair.