Troy/Taj and its role in CNS axon regeneration.
Binding of myelin inhibitors to the NgR1/p75/LINGO-1 signaling complex activates RhoA to mediate the inhibition of axonal outgrowth. The nerve growth factor receptor p75, a TNF family receptor, is absent or poorly expressed in certain types of neurons that respond to myelin inhibitors, thereby prompting speculation that other TNF family receptors are involved in the NgR1 complex. Troy/Taj is an orphan TNF family receptor that is broadly expressed in postnatal and adult neurons. Troy binds to NgR1 and can functionally replace p75 in the p75/NgR1/LINGO-1 complex to activate RhoA and block neurite outgrowth in the presence of myelin inhibitors. Neurons from Troy-deficient mice are more resistant to the suppressive action of the myelin inhibitors. The discovery of TROY function in axon growth is an important step for understanding the complex regulation of axonal regeneration by diverse members of the TNF receptor family.
Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, United States. sha.mi@biogenidec.com
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D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000502:physiology*; D016415:Sequence Alignment
C482293:LINGO1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020800:Receptor, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C411850:TNFRSF19 protein, human; C409471:Tnfrsf19 protein, mouse