A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors.
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.
Park
Jong Bae
JB
Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Yiu
Glenn
G
Kaneko
Shinjiro
S
Wang
Jing
J
Chang
Jufang
J
He
Xiaolin L
XL
Garcia
K Christopher
KC
He
Zhigang
Z
D000367:Age Factors; D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D058851:GPI-Linked Proteins; D006131:Growth Inhibitors / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D009154:Mutation / Q000502:physiology; D009185:Myelin Proteins / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins; D000070816:Nogo Receptor 1; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D058851:GPI-Linked Proteins; D006131:Growth Inhibitors; C482293:LINGO1 protein, human; D008565:Membrane Proteins; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins; D000070816:Nogo Receptor 1; D020800:Receptor, Nerve Growth Factor; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C419790:Rtn4r protein, mouse; C409471:Tnfrsf19 protein, mouse; D020742:rhoA GTP-Binding Protein