TY - JOUR
T1 - NRAGE, a p75NTR adaptor protein, is required for developmental apoptosis in vivo
AU - Bertrand, M. J.M.
AU - Kenchappa, R. S.
AU - Andrieu, D.
AU - Leclercq-Smekens, M.
AU - Nguyen, H. N.T.
AU - Carter, B. D.
AU - Muscatelli, F.
AU - Barker, P. A.
AU - De Backer, O.
N1 - Funding Information:
Acknowledgements. We are grateful to Prof. M Herin for help with hair follicle analysis and to P Auquier, D Desnoeck, C Dernoncourt and R Déom for technical assistance. Dr. Barry Bedell provided valuable help with sympathetic neuron counts and Drs. Peter McPherson and Brigitte Ritter provided the protocol for producing miRNA-expressing lentivirus. This work was supported by Action de Recherche Concertée no 99/03-248 of the Communauté Franc¸aise de Belgique (to ODB), by the Fonds de la Recherche Scientifique et Médicale (Grant no 3.4527.04) of the Fonds National de la Recherche Scientifique of Belgium (to ODB), and by operating funds from the Canadian Institutes of Health Research (to PAB). MB was supported by the Fonds pour la formation à la Recherche dans l′Industrie et l′Agriculture (FNRS of Belgium), DA was supported by the French Association pour la Recherche sur le Cancer (ARC) and PAB is an Investigator of the Canadian Institutes of Health Research.
PY - 2008
Y1 - 2008
N2 - NRAGE (also known as Maged1, Dlxin) is a member of the MAGE gene family that may play a role in the neuronal apoptosis that is regulated by the p75 neurotrophin receptor (p75NTR). To test this hypothesis in vivo, we generated NRAGE knockout mice and found that NRAGE deletion caused a defect in developmental apoptosis of sympathetic neurons of the superior cervical ganglia, similar to that observed in p75NTR knockout mice. Primary sympathetic neurons derived from NRAGE knockout mice were resistant to apoptosis induced by brain-derived neurotrophic factor (BDNF), a pro-apoptotic p75NTR ligand, and NRAGE-deficient sympathetic neurons show attenuated BDNF-dependent JNK activation. Hair follicle catagen is an apoptosis-like process that is dependent on p75NTR signaling; we show that NRAGE and p75NTR show regulated co-expression in the hair follicle and that identical defects in hair follicle catagen are present in NRAGE and p75NTR knockout mice. Interestingly, NRAGE knockout mice have severe defects in motoneuron apoptosis that are not observed in p75NTR knockout animals, raising the possibility that NRAGE may facilitate apoptosis induced by receptors other than p75NTR. Together, these studies demonstrate that NRAGE plays an important role in apoptotic-signaling in vivo.
AB - NRAGE (also known as Maged1, Dlxin) is a member of the MAGE gene family that may play a role in the neuronal apoptosis that is regulated by the p75 neurotrophin receptor (p75NTR). To test this hypothesis in vivo, we generated NRAGE knockout mice and found that NRAGE deletion caused a defect in developmental apoptosis of sympathetic neurons of the superior cervical ganglia, similar to that observed in p75NTR knockout mice. Primary sympathetic neurons derived from NRAGE knockout mice were resistant to apoptosis induced by brain-derived neurotrophic factor (BDNF), a pro-apoptotic p75NTR ligand, and NRAGE-deficient sympathetic neurons show attenuated BDNF-dependent JNK activation. Hair follicle catagen is an apoptosis-like process that is dependent on p75NTR signaling; we show that NRAGE and p75NTR show regulated co-expression in the hair follicle and that identical defects in hair follicle catagen are present in NRAGE and p75NTR knockout mice. Interestingly, NRAGE knockout mice have severe defects in motoneuron apoptosis that are not observed in p75NTR knockout animals, raising the possibility that NRAGE may facilitate apoptosis induced by receptors other than p75NTR. Together, these studies demonstrate that NRAGE plays an important role in apoptotic-signaling in vivo.
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U2 - 10.1038/cdd.2008.127
DO - 10.1038/cdd.2008.127
M3 - Article
C2 - 18772898
AN - SCOPUS:56349161988
SN - 1350-9047
VL - 15
SP - 1921
EP - 1929
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 12
ER -