RRC ID 49598
Author Brosius Lutz A, Chung WS, Sloan SA, Carson GA, Zhou L, Lovelett E, Posada S, Zuchero JB, Barres BA.
Title Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury.
Journal Proc Natl Acad Sci U S A
Abstract Ineffective myelin debris clearance is a major factor contributing to the poor regenerative ability of the central nervous system. In stark contrast, rapid clearance of myelin debris from the injured peripheral nervous system (PNS) is one of the keys to this system's remarkable regenerative capacity, but the molecular mechanisms driving PNS myelin clearance are incompletely understood. We set out to discover new pathways of PNS myelin clearance to identify novel strategies for activating myelin clearance in the injured central nervous system, where myelin debris is not cleared efficiently. Here we show that Schwann cells, the myelinating glia of the PNS, collaborate with hematogenous macrophages to clear myelin debris using TAM (Tyro3, Axl, Mer) receptor-mediated phagocytosis as well as autophagy. In a mouse model of PNS nerve crush injury, Schwann cells up-regulate TAM phagocytic receptors Axl and Mertk following PNS injury, and Schwann cells lacking both of these phagocytic receptors exhibit significantly impaired myelin phagocytosis both in vitro and in vivo. Autophagy-deficient Schwann cells also display reductions in myelin clearance after mouse nerve crush injury, as has been recently shown following nerve transection. These findings add a mechanism, Axl/Mertk-mediated myelin clearance, to the repertoire of cellular machinery used to clear myelin in the injured PNS. Given recent evidence that astrocytes express Axl and Mertk and have previously unrecognized phagocytic potential, this pathway may be a promising avenue for activating myelin clearance after CNS injury.
Volume 114(38)
Pages E8072-E8080
Published 2017-9-19
DOI 10.1073/pnas.1710566114
PII 1710566114
PMID 28874532
PMC PMC5617301
MeSH Animals Autophagy* Axl Receptor Tyrosine Kinase Disease Models, Animal Mice Myelin Sheath / genetics Myelin Sheath / metabolism* Myelin Sheath / pathology Peripheral Nerve Injuries / genetics Peripheral Nerve Injuries / metabolism* Peripheral Nerve Injuries / pathology Phagocytosis* Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism* Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism* c-Mer Tyrosine Kinase / genetics c-Mer Tyrosine Kinase / metabolism*
IF 9.412
Times Cited 47
Mice RBRC00806