Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury

被引:166
作者
Lutz, Amanda Brosius [1 ]
Chung, Won-Suk [2 ]
Sloan, Steven A. [3 ]
Carson, Glenn A. [3 ]
Zhou, Lu [3 ]
Lovelett, Emilie [3 ]
Posada, Sean [3 ]
Zuchero, J. Bradley [4 ]
Barres, Ben A. [3 ]
机构
[1] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA
[2] Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejeon 34141, South Korea
[3] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA
[4] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA
基金
新加坡国家研究基金会;
关键词
myelin; phagocytosis; Wallerian degeneration; Schwann cell; regeneration; WALLERIAN DEGENERATION; APOPTOTIC CELLS; REGENERATION; MOTOR; ASTROCYTES; DEPLETION; HEALTH;
D O I
10.1073/pnas.1710566114
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:E8072 / E8080
页数:9
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