Target-derived neurotrophins regulate neuronal survival and growth by interacting with cell-surface tyrosine kinase receptors. The p75 neurotrophin receptor (p75 NTR) is coexpressed with Trk receptors in long-range projection neurons, in which it facilitates neurotrophin binding to Trk and enhances Trk activity. Here, we show that TrkA and TrkB receptors undergo robust ligand-dependent ubiquitination that is dependent on activation of the endogenous Trk activity of the receptors. Coexpression of p75 NTR attenuated ubiquitination of TrkA and TrkB and delayed nerve growth factor-induced TrkA receptor internalization and receptor degradation. These results indicate that p75 NTR may prolong cell-surface Trk-dependent signalling events by negatively regulating receptor ubiquitination.
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http://dx.doi.org/10.1038/sj.embor.7400503 | DOI Listing |
Int J Mol Sci
December 2024
Department of Otorhinolaryngology, Medical University Innsbruck, 6020 Innsbruck, Austria.
We determined the relative expression levels of the receptors , , , and and ligands , , , and with RNAseq analysis on fetal human inner ear samples, located TrkB and TrkC proteins, and quantified with in situ hybridization on histological sections between gestational weeks (GW) 9 to 19. Spiral ganglion neurons (SGNs) and satellite glia appear to be the main source of and synthesis peaks twice at GW10 and GW15-GW17. Tonotopical gradients of revert between GW8 and GW15 and follow a maturation and innervation density gradient in SGNs.
View Article and Find Full Text PDFCell Signal
December 2024
Research Service, Edward Hines Jr. Veterans Administration Hospital, Hines, IL, USA; Department of Molecular Pharmacology and Neuroscience, Loyola University Chicago, Health Sciences Division, Maywood, IL, USA.
The nerve growth factor (NGF) receptor TrkA is a tightly regulated receptor tyrosine kinase that activates neuronal signaling pathways promoting cell survival in addition to axonal and dendritic outgrowth. Previously, we showed that NGF and TrkA signaling is altered in neuron-like PC12 cells that overexpress Nogo-A, a protein known to influence axonal outgrowth and dendritic arborization associated with neuronal plasticity. In the present report, we provide evidence for changes in NGF-mediated receptor-level and downstream signaling that occur in cells overexpressing Nogo-A.
View Article and Find Full Text PDFNeurotherapeutics
November 2024
Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the HTT gene encoding a mutant huntingtin (mHtt) protein. mHtt aggregates within neurons causing degeneration primarily in the striatum. There is currently a need for disease-modifying treatments for HD.
View Article and Find Full Text PDFMol Psychiatry
November 2024
Department of Pharmacology, School of Medicine, University of Crete, Heraklion, 71003, Greece.
Alzheimer's Disease (AD) is an incurable and debilitating progressive, neurodegenerative disorder which is the leading cause of dementia worldwide. Neuropathologically, AD is characterized by the accumulation of Aβ amyloid plaques in the microenvironment of brain cells and neurovascular walls, chronic neuroinflammation, resulting in neuronal and synaptic loss, myelin and axonal failure, as well as significant reduction in adult hippocampal neurogenesis. The hippocampal formation is particularly vulnerable to this degenerative process, due to early dysfunction of the cholinergic circuit.
View Article and Find Full Text PDFRespir Physiol Neurobiol
November 2024
Master program in Medical Physiology, School of Medicine, Tzu Chi University, Hualien, Taiwan; Department of Physiology, School of Medicine, Tzu Chi University, Hualien, Taiwan. Electronic address:
Obstructive sleep apnea, characterized by airway exposure to intermittent hypoxia (IH), is associated with laryngeal airway hyperreactivity (LAH) and laryngeal inflammation. The sensitization of capsaicin-sensitive superior laryngeal afferents (CSSLAs) by inflammatory mediators has been implicated in the pathogenesis of LAH. Nerve growth factor (NGF) is an inflammatory mediator that acts on tropomyosin receptor kinase A (TrkA) and the p75 neurotrophin receptor (p75) to induce lower airway hyperresponsiveness.
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