Signaling by death receptors in the nervous system

Haase, Georg; Pettmann, Brigitte; Raoul, Cédric; Henderson, Chris

doi:10.1016/j.conb.2008.07.013

Cited by 90 publications

(67 citation statements)

References 56 publications

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“…It has been proposed that dependence receptors thus act mainly as amplifiers of low amounts of caspase activity, which yield to efficient cell death through the release of a part of their intracellular domain that is sufficient to convey death signals. In the case of Unc5 receptors, this intracellular domain bears structural similarities to a death domain structural motif, similar to the one found in p75 and other pro-apoptotic receptors (Frade et al 1996;Haase et al 2008;Llambi et al 2001). Surprisingly, however, the intracellular part of DCC that seems to be necessary and sufficient for apoptotic effects does not bear any homology with such domains.…”

Section: Axon Guidance Molecules and Neural Cell Death Netrins And Thmentioning

confidence: 94%

Guidance Molecules in Axon Pruning and Cell Death

Vanderhaeghen¹,

Cheng²

2010

Cold Spring Harbor Perspectives in Biology

114

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Axon pruning and neuronal cell death constitute two major regressive events that enable the establishment of fully mature brain architecture and connectivity. Although the cellular mechanisms for these two events are thought to be distinct, recent evidence has indicated the direct involvement of axon guidance molecules, including semaphorins, netrins, and ephrins, in controlling both processes. Here, we review how axon guidance cues regulate regressive events in paradigmatic models of neural development, from early control of apoptosis of neural progenitors, to later maintenance of neuronal survival and stereotyped pruning of axonal branches. These new findings are also discussed in the context of neural diseases and the potential links between axon pruning and degeneration. REGRESSIVE EVENTS IN NEURONAL DEVELOPMENT

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Section: Axon Guidance Molecules and Neural Cell Death Netrins And Thmentioning

confidence: 94%

Guidance Molecules in Axon Pruning and Cell Death

Vanderhaeghen¹,

Cheng²

2010

Cold Spring Harbor Perspectives in Biology

114

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“…12 Nerve growth factor in combination with nitric oxide (NO), produced by reactive astrocytes, has been proposed to induce a p75 NTR -dependent motoneuron death in vitro, 13 but conflicting results have not yet demonstrated a functional relevance of p75 NTR in the direct killing of motoneurons in ALS models. 9 We previously demonstrated that Fas triggers a motoneuron-restricted death pathway, which is exacerbated in a cell-autonomous manner by mutant SOD1. 14,15 Interestingly, a functional involvement of the Fas death pathway in motoneuron degeneration in mutant SOD1 mice has been shown.…”

mentioning

confidence: 99%

“…9,10 TNFa can efficiently trigger the death of cultured motoneurons, 11 but may not directly participate to motoneuron degeneration in disease. 12 Nerve growth factor in combination with nitric oxide (NO), produced by reactive astrocytes, has been proposed to induce a p75 NTR -dependent motoneuron death in vitro, 13 but conflicting results have not yet demonstrated a functional relevance of p75 NTR in the direct killing of motoneurons in ALS models.…”

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confidence: 99%

IFNγ triggers a LIGHT-dependent selective death of motoneurons contributing to the non-cell-autonomous effects of mutant SOD1

et al. 2010

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Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that primarily affects motoneurons in the brain and spinal cord. Dominant mutations in superoxide dismutase-1 (SOD1) cause a familial form of ALS. Mutant SOD1-damaged glial cells contribute to ALS pathogenesis by releasing neurotoxic factors, but the mechanistic basis of the motoneuron-specific elimination is poorly understood. Here, we describe a motoneuron-selective death pathway triggered by activation of lymphotoxin-b receptor (LT-bR) by LIGHT, and operating by a novel signaling scheme. We show that astrocytes expressing mutant SOD1 mediate the selective death of motoneurons through the proinflammatory cytokine interferon-c (IFNc), which activates the LIGHT-LT-bR death pathway. The expression of LIGHT and LT-bR by motoneurons in vivo correlates with the preferential expression of IFNc by motoneurons and astrocytes at disease onset and symptomatic stage in ALS mice. Importantly, the genetic ablation of Light in an ALS mouse model retards progression, but not onset, of the disease and increases lifespan. We propose that IFNc contributes to a cross-talk between motoneurons and astrocytes causing the selective loss of some motoneurons following activation of the LIGHT-induced death pathway.

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“…The intracellular region of the p55 tumor necrosis factor receptor, Fas receptor, and p75 contains a death domain sequence (2). The death domain serves as a proteinprotein docking site and is required for initiating tumor necrosis factor-and Fas-mediated apoptosis (3).…”

mentioning

confidence: 99%

“…The p75 receptor is recognized by all the neurotrophins (NGF, 3 brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4), which promote differentiation, growth, and survival of diverse cell types in the nervous system (4 -6). Neurotrophins also initiate signaling through Trk tyrosine kinase receptors, which are capable of forming high affinity binding sites with p75 to potentiate responses at low concentrations of neurotrophins (7).…”

mentioning

confidence: 99%

Nuclear Localization of the p75 Neurotrophin Receptor Intracellular Domain

Parkhurst

Zampieri

Chao

2010

Journal of Biological Chemistry

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The p75 neurotrophin receptor, a member of the tumor necrosis factor superfamily of receptors, undergoes an ␣-secretase-mediated release of its extracellular domain, followed by a ␥-secretase-mediated intramembrane cleavage. Like amyloid precursor protein and Notch, ␥-secretase cleavage of the p75 receptor releases an intracellular domain (ICD). However, it has been experimentally challenging to determine the precise subcellular localization and functional consequences of the p75 ICD. Here, we utilized a nuclear translocation assay and biochemical fractionation approaches to follow the fate of the ICD. We found that the p75 ICD can translocate to the nucleus to activate a green fluorescent protein reporter gene. Furthermore, the p75 ICD was localized in nuclear fractions. Chromatin immunoprecipitation experiments indicated that nerve growth factor induced the association of endogenous p75 with the cyclin E 1 promoter. Expression of the p75 ICD resulted in modulation of gene expression from this locus. These results suggest that the p75 ICD generated by ␥-secretase cleavage is capable of modulating transcriptional events in the nucleus.The p75 neurotrophin receptor is the founding member of the tumor necrosis factor receptor superfamily that includes the Fas antigen, DR6, CD30, and CD40. This family of receptors is distinguished with multiple cysteine-rich domains for ligand binding, a single transmembrane sequence, and a noncatalytic cytoplasmic domain (1). The intracellular region of the p55 tumor necrosis factor receptor, Fas receptor, and p75 contains a death domain sequence (2). The death domain serves as a proteinprotein docking site and is required for initiating tumor necrosis factor-and Fas-mediated apoptosis (3).The p75 receptor is recognized by all the neurotrophins (NGF, 3 brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4), which promote differentiation, growth, and survival of diverse cell types in the nervous system (4 -6). Neurotrophins also initiate signaling through Trk tyrosine kinase receptors, which are capable of forming high affinity binding sites with p75 to potentiate responses at low concentrations of neurotrophins (7). The precursor form of neurotrophins (proneurotrophins) binds more avidly to p75 than the mature form (8, 9). In the absence of Trk receptors, p75 is capable of independent signaling that activates NF-B, c-Jun N-terminal kinase (JNK), and the sphingomyelin cycle (10). In selected cell types, p75 can initiate cell death (11-13). Alternatively, p75 can serve as a co-receptor for several proteins that modulate axon outgrowth, such as Nogo, neuropilin-1, and plexin-A4 (14 -16). Recently, p75 interaction with ephrin A has been shown to direct targeting of retinal ganglion cells during development (17).Intramembrane cleavage events have been detected for p75 in many cell types (18,19). Proteolysis through presenilin-dependent ␥-secretase activity has emerged as a highly conserved and prevalent mechanism in receptor signaling responsible for the intramembrane c...

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Signaling by death receptors in the nervous system

Cited by 90 publications

References 56 publications

Guidance Molecules in Axon Pruning and Cell Death

Guidance Molecules in Axon Pruning and Cell Death

IFNγ triggers a LIGHT-dependent selective death of motoneurons contributing to the non-cell-autonomous effects of mutant SOD1

Nuclear Localization of the p75 Neurotrophin Receptor Intracellular Domain

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