Nogo receptor antagonizes p75NTR-dependent motor neuron death

doi:10.1073/pnas.0703842105

Nogo receptor antagonizes p75NTR-dependent motor neuron death

*Institut National de la Santé et de la Recherche Médicale, U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, Strasbourg, F-67085 France;
^†Université Louis Pasteur, Faculté de Médecine, UMRS692, Strasbourg, F-67085 France;
^‡Departamento de Neurobiología Celular, Institut Pasteur, Montevideo, 11600 Uruguay;
^§Faculdad de Medicina, Universidad de la República, Montevideo, 11800 Uruguay; and
^¶Brain Research Institute, University of Zurich and Department of Biology, Eidgenössiche Technische Hochschule, Zurich, 8057 Switzerland

Edited by Don W. Cleveland, University of California at San Diego, La Jolla, CA, and approved November 28, 2007 (received for review April 26, 2007)

Abstract

The Nogo-66 receptor (NgR) plays a critical role in restricting axon regeneration in the central nervous system. This inhibitory action is in part mediated by a neuronal receptor complex containing p75NTR, a multifunctional receptor also well known to trigger cell death upon binding to neurotrophins such as NGF. In the present study, we show that Pep4 and NEP1–40, which are two peptides derived from the Nogo-66 sequence that modulate NgR-mediated neurite outgrowth inhibition, prevent NGF-stimulated p75NTR-dependent death of cultured embryonic motor neurons. They also confer protection on spinal cord motor neurons after neonatal sciatic nerve axotomy. These findings demonstrate an as-yet-unknown function of NgR in maintaining neuronal survival that may be relevant for motor neuron development and degeneration.

Footnotes

^‖To whom correspondence should be addressed. E-mail: gonzalez{at}neurochem.u-strasbg.fr
Author contributions: L. Dupuis and M.P. contributed equally to this work; L. Dupuis, M.P., P.C., J.-P.L., L.B., and J.-L.G.d.A. designed research; L. Dupuis, M.P., P.C., F.R., R.C., C.R., and M.G. performed research; L. Dimou and M.E.S. contributed new reagents/analytic tools; L. Dupuis, M.P., P.C., J.-P.L., L.B., and J.-L.G.d.A. analyzed data; and L. Dupuis and J.-L.G.d.A. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0703842105/DC1.