TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration

Zhaohui Shao; Jeffrey L Browning; Xinhua Lee; Martin L Scott; Sveltlana Shulga-Morskaya; Norm Allaire; Greg Thill; Melissa Levesque; Dinah Sah; John M McCoy; Beth Murray; Vincent Jung; R Blake Pepinsky; Sha Mi

doi:10.1016/j.neuron.2004.12.050

TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration

Neuron. 2005 Feb 3;45(3):353-9. doi: 10.1016/j.neuron.2004.12.050.

Authors

Zhaohui Shao¹, Jeffrey L Browning, Xinhua Lee, Martin L Scott, Sveltlana Shulga-Morskaya, Norm Allaire, Greg Thill, Melissa Levesque, Dinah Sah, John M McCoy, Beth Murray, Vincent Jung, R Blake Pepinsky, Sha Mi

Affiliation

¹ Department of Discovery Biology, Biogen Idec, Inc., 14 Cambridge Center, Cambridge, MA 02142, USA.

PMID: 15694322
DOI: 10.1016/j.neuron.2004.12.050

Abstract

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.

MeSH terms

Animals
Axons / physiology
Binding Sites / physiology
CHO Cells
COS Cells
Cell Differentiation / drug effects
Cell Differentiation / physiology
Cricetinae
GPI-Linked Proteins
Growth Inhibitors / metabolism*
Ligands
Macromolecular Substances / metabolism
Membrane Proteins
Mice
Mice, Knockout
Myelin Proteins / metabolism*
Myelin Sheath / metabolism*
Myelin-Associated Glycoprotein / metabolism
Nerve Regeneration / physiology*
Nerve Tissue Proteins
Neurites / drug effects
Neurites / metabolism
Nogo Receptor 1
Receptor, Nerve Growth Factor
Receptors, Cell Surface / metabolism*
Receptors, Nerve Growth Factor / metabolism
Receptors, Tumor Necrosis Factor / genetics
Receptors, Tumor Necrosis Factor / metabolism*
rhoA GTP-Binding Protein / metabolism

Substances

GPI-Linked Proteins
Growth Inhibitors
LINGO1 protein, human
Ligands
Macromolecular Substances
Membrane Proteins
Myelin Proteins
Myelin-Associated Glycoprotein
Nerve Tissue Proteins
Nogo Receptor 1
Receptor, Nerve Growth Factor
Receptors, Cell Surface
Receptors, Nerve Growth Factor
Receptors, Tumor Necrosis Factor
Rtn4r protein, mouse
Tnfrsf19 protein, mouse
rhoA GTP-Binding Protein