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-depen...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2007-08, Vol.104 (33), p.13361-13366
Hauptverfasser: Tauszig-Delamasure, Servane, Yu, Li-Ying, Cabrera, Jorge Ruben, Bouzas-Rodriguez, Jimena, Mermet-Bouvier, Catherine, Guix, Catherine, Bordeaux, Marie-Claire, Arumäe, Urmas, Mehlen, Patrick
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Sprache:eng
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Zusammenfassung: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0701243104