TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration.
Myelin-associated inhibitory factors (MAIFs) are inhibitors of CNS axonal regeneration following injury. The Nogo receptor complex, composed of the Nogo-66 receptor 1 (NgR1), neurotrophin p75 receptor (p75), and LINGO-1, represses axon regeneration upon binding to these myelin components. The limited expression of p75 to certain types of neurons and its temporal expression during development prompted speculation that other receptors are involved in the NgR1 complex. Here, we show that an orphan receptor in the TNF family called TAJ, broadly expressed in postnatal and adult neurons, binds to NgR1 and can replace p75 in the p75/NgR1/LINGO-1 complex to activate RhoA in the presence of myelin inhibitors. In vitro exogenously added TAJ reversed neurite outgrowth caused by MAIFs. Neurons from Taj-deficient mice were more resistant to the suppressive action of the myelin inhibitors. Given the limited expression of p75, the discovery of TAJ function is an important step for understanding the regulation of axonal regeneration.
Shao
Zhaohui
Z
Department of Discovery Biology, Biogen Idec, Inc., 14 Cambridge Center, Cambridge, MA 02142, USA.
Browning
Jeffrey L
JL
Lee
Xinhua
X
Scott
Martin L
ML
Shulga-Morskaya
Sveltlana
S
Allaire
Norm
N
Thill
Greg
G
Levesque
Melissa
M
Sah
Dinah
D
McCoy
John M
JM
Murray
Beth
B
Jung
Vincent
V
Pepinsky
R Blake
RB
Mi
Sha
S
D000818:Animals; D001369:Axons / Q000502:physiology; D001665:Binding Sites / Q000502:physiology; D016466:CHO Cells; D019556:COS Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D058851:GPI-Linked Proteins; D006131:Growth Inhibitors / Q000378:metabolism*; D008024:Ligands; D046911:Macromolecular Substances / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D000070816:Nogo Receptor 1; D020800:Receptor, Nerve Growth Factor; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D058851:GPI-Linked Proteins; D006131:Growth Inhibitors; C482293:LINGO1 protein, human; D008024:Ligands; D046911:Macromolecular Substances; 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; C419790:Rtn4r protein, mouse; C409471:Tnfrsf19 protein, mouse; D020742:rhoA GTP-Binding Protein