QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 17, 2004, 24(46):10521-10529; doi:10.1523/JNEUROSCI.1390-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (18) Citing Articles via Google Scholar Google Scholar Articles by Yeiser, E. C. Articles by Carter, B. D. Search for Related Content PubMed PubMed Citation Articles by Yeiser, E. C. Articles by Carter, B. D.

 Previous Article  |  Next Article 

Cellular/Molecular
Neurotrophin Signaling through the p75 Receptor Is Deficient in traf6-/- Mice

E. Carden Yeiser,¹ Nancy J. Rutkoski,¹ Asuka Naito,² Jun-ichiro Inoue,² and Bruce D. Carter¹

¹Department of Biochemistry and Center for Molecular Neuroscience, Vanderbilt University Medical School, Nashville, Tennessee 37232, and ²Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

Activation of the neurotrophin receptor p75 has been shown to elicit opposing cellular signals. Depending on the context of the cell, p75 will either promote survival or induce apoptosis after neurotrophin stimulation. p75-induced apoptosis occurs through activation of c-Jun N-terminal kinase (JNK), whereas the survival signal is mediated by nuclear factor B (NFB). The receptor proximal signals that produce these responses are unknown, although several molecules have been identified that associate with the intracellular domain of p75. One such interactor, TRAF6, a member of the tumor necrosis factor receptor-associated factor family, has been implicated in p75 signaling. To assess the role of TRAF6 in p75 signaling, we analyzed mice with this gene deleted. In Schwann cells isolated from traf6+/+ animals, NGF elicited an 80% increase in transcription of an NFB reporter; however, in traf6-/- cells, the NGF response was abrogated. Similarly, NGF activation of JNK was not apparent in Schwann cells from mice lacking traf6. Deficiencies in p75 signaling in traf6-/- animals resulted in a loss of p75-mediated apoptosis. In sympathetic neurons cultured from traf6+/+ superior cervical ganglia (SCGs), there was an increase in JNK activation and apoptosis after BDNF binding to p75; however, traf6-/- neurons did not respond. In vivo during naturally occurring cell death, there was a 55.6% reduction in TUNEL (terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling)-positive cells in the SCG of postnatal day 4 traf6-/- animals relative to traf6+/+ littermates. These results indicate that TRAF6 plays an essential role in mediating p75 signal transduction and induction of apoptosis.

Key words: NGF; BDNF; TNF; neuron; apoptosis; NFB

---

Received Nov 25, 2003; revised October 6, 2004; accepted October 14, 2004.

This article has been cited by other articles:

				A. Caporali and C. Emanueli Cardiovascular Actions of Neurotrophins Physiol Rev, January 1, 2009; 89(1): 279 - 308. [Abstract] [Full Text] [PDF]

				C. D. Deppmann, S. Mihalas, N. Sharma, B. E. Lonze, E. Niebur, and D. D. Ginty A Model for Neuronal Competition During Development Science, April 18, 2008; 320(5874): 369 - 373. [Abstract] [Full Text] [PDF]

				M. M. Lino, S. Atanasoski, M. Kvajo, B. Fayard, E. Moreno, H. R. Brenner, U. Suter, and D. Monard Mice Lacking Protease Nexin-1 Show Delayed Structural and Functional Recovery after Sciatic Nerve Crush J. Neurosci., April 4, 2007; 27(14): 3677 - 3685. [Abstract] [Full Text] [PDF]

				L. F Reichardt Neurotrophin-regulated signalling pathways Phil Trans R Soc B, September 29, 2006; 361(1473): 1545 - 1564. [Abstract] [Full Text] [PDF]

				J. P. Aurikko, B. T. Ruotolo, J. G. Grossmann, M. C. Moncrieffe, E. Stephens, V.-M. Leppanen, C. V. Robinson, M. Saarma, R. A. Bradshaw, and T. L. Blundell Characterization of Symmetric Complexes of Nerve Growth Factor and the Ectodomain of the Pan-neurotrophin Receptor, p75NTR J. Biol. Chem., September 30, 2005; 280(39): 33453 - 33460. [Abstract] [Full Text] [PDF]

				M. S. Linggi, T. L. Burke, B. B. Williams, A. Harrington, R. Kraemer, B. L. Hempstead, S. O. Yoon, and B. D. Carter Neurotrophin Receptor Interacting Factor (NRIF) Is an Essential Mediator of Apoptotic Signaling by the p75 Neurotrophin Receptor J. Biol. Chem., April 8, 2005; 280(14): 13801 - 13808. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help