The p75 neurotrophin receptor and neuronal apoptosis

Barrett, Graham L.

doi:10.1016/s0301-0082(99)00056-8

Cited by 210 publications

(130 citation statements)

References 133 publications

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“…These studies show that p75 NTR engages multiple and sometimes opposing signaling pathways, depending on the cell type, microenvironment, and stage of development (10). Invariably, cellular systems developed to study p75 NTR function and mechanisms show only a subset of the responses attributed to p75 NTR signaling.…”

Section: Resultsmentioning

confidence: 99%

“…10). These heterotypic interactions are mediated by both the intracellular and the extracellular domains of both receptors.…”

Section: Discussionmentioning

confidence: 99%

“…The neurotrophin family includes NGF, brain-derived neurotrophic factor, neurotrophin-3 (NT-3), NT-4/5, and NTR binds all neurotrophins with low affinity, but ligandinduced signaling has only been shown repeatedly for NGF (10) and in single reports for brain-derived neurotrophic factor (7) and NT4 (11).…”

mentioning

confidence: 99%

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Characterization of a p75NTR Apoptotic Signaling Pathway Using a Novel Cellular Model

Wang¹,

Bauer²,

Li³

et al. 2001

Journal of Biological Chemistry

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The p75 neurotrophin receptor (p75 NTR ) belongs to the tumor necrosis factor receptor/nerve growth factor receptor superfamily. In some cells derived from neuronal tissues it causes cell death through a poorly characterized pathway. We developed a neuronal system using conditionally immortalized striatal neurons, in which the expression of p75 NTR is inducibly controlled by the ecdysone receptor. In these cells p75 NTR induces apoptosis through its death domain in a nerve growth factor-independent manner. Caspases 9, 6, and 3 are activated by receptor expression indicating the activation of the common effector pathway of apoptosis. Cell death is blocked by a dominant negative form of caspase 9 and Bcl-X L consistent with a pathway that involves mitochondria. Significantly, the viral flice inhibitory protein E8 protects from p75 NTR -induced cell death indicating that death effector domains are involved. A p75 NTR construct with a deleted death domain dominantly interferes with p75 NTR signaling, implying that receptor multimerization is required. However, in contrast to the other receptors of the family, p75 NTR -mediated apoptosis does not involve the adaptor proteins Fas-associated death domain protein or tumor necrosis factor-associated death domain protein, and the apical caspase 8 is not activated. We conclude that p75 NTR signals apoptosis by similar mechanisms as other death receptors but uses different adaptors and apical caspases.

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Section: Resultsmentioning

confidence: 99%

“…10). These heterotypic interactions are mediated by both the intracellular and the extracellular domains of both receptors.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of a p75NTR Apoptotic Signaling Pathway Using a Novel Cellular Model

Wang¹,

Bauer²,

Li³

et al. 2001

Journal of Biological Chemistry

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“…These NTs interact with two classes of membrane bound receptors, namely the common NT receptor p75NTR, a member of the tumor necrosis factor (TNF) receptor gene family that is expressed in neuronal and non-neuronal tissues (Dechant and Barde, 2002;Hempstead, 2002;Roux and Barker, 2002), and members of the TRK gene family, which are expressed in the developing and mature nervous system (Huang and Reichardt, 2001; Lee et al, 2001). The functions of p75NTR include, but are not limited to, induction of apoptosis or survival, regulation of axon myelination and axon regeneration (Barrett, 2000;Beattie et al, 2002;Cosgaya et al, 2002;Dechant and Barde, 2002;Wang et al, 2002). The role of p75NTR in NB is unclear, yet the receptor can complex with TRKA to strengthen the NGF signal, which may contribute to NB differentiation.…”

Section: Introductionmentioning

confidence: 99%

The RET and TRKA pathways collaborate to regulate neuroblastoma differentiation

Peterson

Bogenmann

2004

Oncogene

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Neuroblastoma (NB) is a childhood cancer that arises in the adrenal gland and often shows differentiated neuronal and glial elements. The RET receptor signal pathway is functional in most NB, while loss of nerve growth factor (NGF) receptor (trkA) gene expression correlates with an aggressive phenotype. Thus, we hypothesized that the RET and TRKA signal pathways collaborate to instruct NB differentiation, reminiscent of normal neuronal maturation. Here, we demonstrate that activation of the RET receptor by glial cell line-derived neurotrophic factor (GDNF) increases expression of the RET receptor complex in a panel of malignant human NB cell lines, indicative of a positive feedback mechanism. GDNF also induces growth cessation concomitant with an arrest of cells in the G 0 /G 1 phase of the cell cycle. Furthermore, GDNF synergizes with ciliary neurotrophic factor (CNTF) to enhance TRKA receptor expression, thereby strengthening the NGF-mediated differentiation signal. Differentiated NB cells downregulate expression of the amplified N-myc gene, concurrent with the arrest of cell proliferation, while expressing neuron-specific markers (i.e., SCG10). Interestingly, maintenance of differentiated NB cells in culture is independent of the trophic activity of GDNF, but depends on TRKA signaling, thereby reenacting the differentiation of normal sympathoadrenal (SA) progenitor cells.

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“…10 In contrast, the role of p75 NTR is poorly understood, and may depend on the cellular context in which it is expressed. 11,12 When coexpressed with TrkA, p75 NTR can augment the trophic effects of NGF by enhancing TrkA autophosphorylation, and affinity for NGF binding. 13,14 On the other hand, in cells which express only p75 NTR , NGF may mediate a signaling cascade which leads to apoptotic cell death, 6 ± 8 although this does not always occur.…”

Section: Introductionmentioning

confidence: 99%

Zinc inhibits p75NTR-mediated apoptosis in chick neural retina

et al. 2001

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It has previously been documented that Zn 2+ inhibits TrkAmediated effects of NGF. To evaluate the ability of Zn 2+ to attenuate the biological activities of NGF mediated by p75 NTR , we characterized the effects of this transition metal cation on both binding and the pro-apoptotic properties of the NGFp75 NTR interaction. Binding of NGF to p75 NTR displayed higher affinity in embryonic chick retinal cells than in PC12 cells. NGF induced apoptosis in dissociated cultures of chick neural retina. The addition of 100 mM Zn 2+ inhibited binding and chemical cross-linking of 125 I-NGF to p75 NTR , and also attenuated apoptosis mediated by this ligand-receptor interaction. These studies lead to the conclusion that Zn 2+ antagonizes NGF/p75 NTR -mediated signaling, suggesting that the effect of this transition metal cation can be either pro-or anti-apoptotic depending on the cellular context. Cell Death and Differentiation (2001) 8, 451 ± 456.

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The p75 neurotrophin receptor and neuronal apoptosis

Cited by 210 publications

References 133 publications

Characterization of a p75NTR Apoptotic Signaling Pathway Using a Novel Cellular Model

Characterization of a p75NTR Apoptotic Signaling Pathway Using a Novel Cellular Model

The RET and TRKA pathways collaborate to regulate neuroblastoma differentiation

Zinc inhibits p75NTR-mediated apoptosis in chick neural retina

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