The TrkC receptor induces apoptosis when the dependence receptor notion meets the neurotrophin paradigm.
The TrkC/NT-3 receptor/ligand pair is believed to be part of the classic neurotrophic theory claiming that neuronal death occurs by default when neurotrophic factors become limited, through loss of survival signals. Here, we show that TrkC is a dependence receptor and, as such, induces caspase-dependent apoptotic death in the absence of NT-3 in immortalized cells, a proapoptotic activity inhibited by the presence of NT-3. This proapoptotic activity of TrkC relies on the caspase-mediated cleavage of the intracellular domain of TrkC, which permits the release of a proapoptotic fragment. This fragment induces apoptosis through a caspase-9-dependent mechanism. Finally, we show that the death of dorsal root ganglion (DRG) neurons provoked by NT-3 withdrawal is inhibited when TrkC-proapoptotic activity is antagonized. Thus, the death of neurons upon disappearance of NT-3 is not only due to a loss of survival signals but also to the active proapoptotic activity of the unbound TrkC dependence receptor.
Apoptosis, Cancer and Development Laboratory, Equipe Labellisée La Ligue, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5238, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.
Servane
S
Tauszig-Delamasure
Li-Ying
LY
Yu
Jorge Ruben
JR
Cabrera
Jimena
J
Bouzas-Rodriguez
Catherine
C
Mermet-Bouvier
Catherine
C
Guix
Marie-Claire
MC
Bordeaux
Urmas
U
Arumäe
Patrick
P
Mehlen
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D009474:Neurons / Q000166:cytology; D051381:Rats; D020812:Receptor, trkC / Q000502:physiology*
D020812:Receptor, trkC; D020169:Caspases