Stoichiometry counts

Chao, Moses V.

doi:10.1073/pnas.1914583116

Cited by 2 publications

(3 citation statements)

References 29 publications

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“…A critical and controversial question in NGF signaling is whether the TrkA and p75 NTR receptors combine in heteromeric complexes 30,34,36 and cooperate or compete, resulting in new features compared to the simple sum of pathways activated by either TrkA and p75 NTR receptor alone.…”

Section: Trka-p75 Ntr Interplaymentioning

confidence: 99%

“…Thus, the physical or functional cooperation of p75 NTR with TrkA is recognized to be a cellular process of paramount importance. On the contrary, the interaction mode and stoichiometry of TrkA and p75 NTR in the absence or presence of NGF stimulation are still a matter of hot debate 30,34,35,36 …”

Section: Introductionmentioning

confidence: 99%

“…On the contrary, the interaction mode and stoichiometry of TrkA and p75 NTR in the absence or presence of NGF stimulation are still a matter of hot debate. 30,34,35,36 Through the years, several studies on this cooperation were carried out using PC12 cells. [37][38][39] This cell line, which was established from a rat pheochromocytoma, is a gold standard model for assessing the biological activity of NGF in vitro, 40 owing to the expression of both NGF receptors.…”

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confidence: 99%

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Disentangling the signaling complexity of nerve growth factor receptors by CRISPR/Cas9

et al. 2022

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NGF-mediated signaling regulates the development and physiology of a wide variety of cells, 1 such as sensory and sympathetic neurons, 2,3 cholinergic neurons, 4 glial, 5 and microglia cells, 6 as well as non-neuronal cells of epithelia, vessels, muscles, endocrine tissues, 7 and of the immune system. 8,9 In recent years, the role of NGF signaling has received increasing attention aiming at diverse clinical applications, including cancer, 10

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Section: Trka-p75 Ntr Interplaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Disentangling the signaling complexity of nerve growth factor receptors by CRISPR/Cas9

et al. 2022

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TrkA-mediated endocytosis of p75-CTF prevents cholinergic neuron death upon γ-secretase inhibition

et al. 2021

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γ-secretase inhibitors (GSI) were developed to reduce the generation of Aβ peptide to find new Alzheimer’s disease treatments. Clinical trials on Alzheimer’s disease patients, however, showed several side effects that worsened the cognitive symptoms of the treated patients. The observed side effects were partially attributed to Notch signaling. However, the effect on other γ-secretase substrates, such as the p75 neurotrophin receptor (p75NTR) has not been studied in detail. p75NTR is highly expressed in the basal forebrain cholinergic neurons (BFCNs) during all life. Here, we show that GSI treatment induces the oligomerization of p75CTF leading to the cell death of BFCNs, and that this event is dependent on TrkA activity. The oligomerization of p75CTF requires an intact cholesterol recognition sequence (CRAC) and the constitutive binding of TRAF6, which activates the JNK and p38 pathways. Remarkably, TrkA rescues from cell death by a mechanism involving the endocytosis of p75CTF. These results suggest that the inhibition of γ-secretase activity in aged patients, where the expression of TrkA in the BFCNs is already reduced, could accelerate cholinergic dysfunction and promote neurodegeneration.

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Stoichiometry counts

Cited by 2 publications

References 29 publications

Disentangling the signaling complexity of nerve growth factor receptors by CRISPR/Cas9

Disentangling the signaling complexity of nerve growth factor receptors by CRISPR/Cas9

TrkA-mediated endocytosis of p75-CTF prevents cholinergic neuron death upon γ-secretase inhibition

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