Nogo receptor antagonizes p75NTR-dependent motor neuron death.
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.
Dupuis
Luc
L
Institut National de la Santé et de la Recherche Médicale, U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, Strasbourg, F-67085 France.
Pehar
Mariana
M
Cassina
Patricia
P
Rene
Frédérique
F
Castellanos
Raquel
R
Rouaux
Caroline
C
Gandelman
Mandi
M
Dimou
Leda
L
Schwab
Martin E
ME
Loeffler
Jean-Philippe
JP
Barbeito
Luis
L
Gonzalez de Aguilar
Jose-Luis
JL
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D016923:Cell Death; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism / Q000502:physiology*; D009410:Nerve Degeneration / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism; D000070816:Nogo Receptor 1; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism*
D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C419790:Rtn4r protein, mouse; C486581:Rtn4r protein, rat; C517634:Ngfr protein, mouse; C068313:Ngfr protein, rat; D020932:Nerve Growth Factor