A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors

Jong Bae Park, Glenn C Yiu, Shinjiro Kaneko, Jing Wang, Jufang Chang, Zhigang He

Research output: Contribution to journalArticlepeer-review

319 Scopus citations

Abstract

A major obstacle for successful axon regeneration in the adult central nervous system (CNS) arises from inhibitory molecules in CNS myelin, which signal through a common receptor complex on neurons consisting of the ligand-binding Nogo-66 receptor (NgR) and two transmembrane coreceptors, p75 and LINGO-1. However, p75 expression is only detectable in subpopulations of mature neurons, raising the question of how these inhibitory signals are transduced in neurons lacking p75. In this study, we demonstrate that TROY (also known as TAJ), a TNF receptor family member selectively expressed in the adult nervous system, can form a functional receptor complex with NgR and LINGO-1 to mediate cellular responses to myelin inhibitors. Also, both overexpressing a dominant-negative TROY or presence of a soluble TROY protein can efficiently block neuronal response to myelin inhibitors. Our results implicate TROY in mediating myelin inhibition, offering new insights into the molecular mechanisms of regeneration failure in the adult nervous system.

Original languageEnglish (US)
Pages (from-to)345-351
Number of pages7
JournalNeuron
Volume45
Issue number3
DOIs
StatePublished - Feb 3 2005
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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