RGM and its receptor neogenin regulate neuronal survival.
Repulsive guidance molecule (RGM) is an axon guidance protein that repels retinal axons upon activation of the neogenin receptor. To understand the functions of RGM-neogenin complexes in vivo, we used gene transfer technology to perturb their expression in the developing neural tube of chick embryos. Surprisingly, neogenin over-expression or RGM down-expression in the neural tube induces apoptosis. Neogenin pro-apoptotic activity in immortalized neuronal cells and in the neural tube is associated with the cleavage of its cytoplasmic domain by caspases. Thus neogenin is a dependence receptor inducing cell death in the absence of RGM, whereas the presence of RGM inhibits this effect.
Matsunaga
Eiji
E
UMR CNRS 7102, Université Paris 6, 9 Quai Saint Bernard, 75005 Paris, France.
Tauszig-Delamasure
Servane
S
Monnier
Philippe P
PP
Mueller
Bernhard K
BK
Strittmatter
Stephen M
SM
Mehlen
Patrick
P
Chédotal
Alain
A
D000818:Animals; D017209:Apoptosis; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D015536:Down-Regulation; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008164:Luminescent Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats
D030161:Avian Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C091279:neogenin; D049452:Green Fluorescent Proteins; D020169:Caspases