RESUMEN
The low affinity neurotrophin receptor (p75(NTR)) is implicated in promoting oligodendrocytic death after nerve growth factor (NGF) stimulation but NGF and neurotrophin-3 (NT-3) can also potentiate oligodendrocytic survival. We show regional variability in p75(NTR) expression within the central nervous system of the postnatal rat; expression is readily detectable by immunohistochemistry upon a subset of CNPase-positive oligodendroglia in optic nerve but not within the cerebrum. Nevertheless, oligodendroglia isolated from the cerebrum and cultured for 16 hours express p75(NTR) as well as the trkC but not the TrkA gene. Viability was not, however, influenced by exposure to either NGF or NT-3. Cells overexpressing p75(NTR) remained unresponsive to NGF but exhibited potentiated survival with NT-3, correlating with the differential expression profile of their high affinity receptors.
Asunto(s)
Corteza Cerebral/citología , Oligodendroglía/fisiología , Receptores de Factor de Crecimiento Nervioso/genética , Adenoviridae/genética , Animales , Animales Recién Nacidos , Células Cultivadas , Regulación del Desarrollo de la Expresión Génica , Vectores Genéticos , Inmunohistoquímica , Operón Lac , Oligodendroglía/química , Oligodendroglía/citología , ARN Mensajero/análisis , Ratas , Ratas Wistar , Receptor de Factor de Crecimiento Nervioso/análisis , Receptor de Factor de Crecimiento Nervioso/genética , Receptor trkA/genética , Receptor trkC/análisis , Receptor trkC/genética , Receptores de Factor de Crecimiento Nervioso/análisisRESUMEN
The cytoplasmic juxtamembrane region of the p75 neurotrophin receptor (p75(NTR)) has been found to be necessary and sufficient to initiate neural cell death. The region was named "Chopper" to distinguish it from CD95-like death domains. A 29-amino acid peptide corresponding to the Chopper region induced caspase- and calpain-mediated death in a variety of neural and non-neural cell types and was not inhibited by signaling through Trk (unlike killing by full-length p75(NTR)). Chopper triggered cell death only when bound to the plasma membrane by a lipid anchor, whereas non-anchored Chopper acted in a dominant-negative manner, blocking p75(NTR)-mediated death both in vitro and in vivo. Removal of the ectodomain of p75(NTR) increased the potency of Chopper activity, suggesting that it regulates the association of Chopper with downstream signaling proteins.